Metal complexes of substituted Gable porphyrins as oxidation catalysts

DOEpatents

Lyons, James E.; Ellis, Jr., Paul E.; Wagner, Richard W.

1996-01-01

Transition metal complexes of Gable porphyrins having two porphyrin rings connected through a linking group, and having on the porphyrin rings electron-withdrawing groups, such as halogen, nitro or cyano. These complexes are useful as catalysts for the oxidation of organic compounds, e.g. alkanes.

Balancing the Hydrogen Evolution Reaction, Surface Energetics, and Stability of Metallic MoS2 Nanosheets via Covalent Functionalization.

PubMed

Benson, Eric E; Zhang, Hanyu; Schuman, Samuel A; Nanayakkara, Sanjini U; Bronstein, Noah D; Ferrere, Suzanne; Blackburn, Jeffrey L; Miller, Elisa M

2018-01-10

We modify the fundamental electronic properties of metallic (1T phase) nanosheets of molybdenum disulfide (MoS 2 ) through covalent chemical functionalization, and thereby directly influence the kinetics of the hydrogen evolution reaction (HER), surface energetics, and stability. Chemically exfoliated, metallic MoS 2 nanosheets are functionalized with organic phenyl rings containing electron donating or withdrawing groups. We find that MoS 2 functionalized with the most electron donating functional group (p-(CH 3 CH 2 ) 2 NPh-MoS 2 ) is the most efficient catalyst for HER in this series, with initial activity that is slightly worse compared to the pristine metallic phase of MoS 2 . The p-(CH 3 CH 2 ) 2 NPh-MoS 2 is more stable than unfunctionalized metallic MoS 2 and outperforms unfunctionalized metallic MoS 2 for continuous H 2 evolution within 10 min under the same conditions. With regards to the entire studied series, the overpotential and Tafel slope for catalytic HER are both directly correlated with the electron donating strength of the functional group. The results are consistent with a mechanism involving ground-state electron donation or withdrawal to/from the MoS 2 nanosheets, which modifies the electron transfer kinetics and catalytic activity of the MoS 2 nanosheet. The functional groups preserve the metallic nature of the MoS 2 nanosheets, inhibiting conversion to the thermodynamically stable semiconducting state (2H) when mildly annealed in a nitrogen atmosphere. We propose that the electron density and, therefore, reactivity of the MoS 2 nanosheets are controlled by the attached functional groups. Functionalizing nanosheets of MoS 2 and other transition metal dichalcogenides provides a synthetic chemical route for controlling the electronic properties and stability within the traditionally thermally unstable metallic state.

Synthesis and carbon-13 NMR studies of liquid crystals

NASA Astrophysics Data System (ADS)

Sun, Hong

2000-08-01

The orientation of different segments of 4'-cyanophenyl 4-heptylbenzoate (7CPB) has been investigated using 13C NMR. The method of proton encoded local field (PELF) spectroscopy was used in combination with off-magic-angle spinning (OMAS) of the sample. High-resolution 2D spectra were obtained and the order parameters were calculated from the spectra. Linear relationships between the obtained order parameters and anisotropic chemical shifts determined by 1D 13C NMR were established and semi-empirical parameters were obtained. A 1:2 mixture of 7CPB and its chain-perfluorinated analog (7PFCPB) shows interesting phase behavior with changing of temperature. The mixture was studied by the use of 13C NMR and polarizing optical microscopy. The order parameters of 7CPB in the smectic A phase of the mixture were calculated using the semi-empirical parameters obtained by the 2D NMR method. Eight series of liquid crystals containing an electron- donating group at one end of a conjugated system and an electron-withdrawing group at the other end have been synthesized. The electron-donating group is 4- n-alkylpiperazinyl group, the electron- withdrawing group is nitro group and the conjugated system is diphenyldiazene with zero, one or two substituents on the phenyl rings. The substituents are -F, -Cl, and -CH3. Two series of compounds with cyano group as electron-withdrawing group were also synthesized. Most of the compounds synthesized are nematogenic and exhibit rather broad liquid crystalline ranges. The effects of the lateral substituents on the optical absorption and phase transition temperatures are correlated with their nature and position of substitution. Birefringence, dielectric anisotropy, elastic constant ratio and rise time of the liquid crystals were carried out using 10 wt% LC mixtures in E7. It has been found that lateral substituents have subtle effects on the properties. The presence of lateral substituents depresses melting points and clearing points of the liquid crystals. All the liquid crystals synthesized in this work have relatively large values of birefiringence, although the dielectric anisotropy values were not as high as desired. The incorporation of a fluorine atom onto the position neighboring the nitro group enhances the conjugation of the push-pull system and liquid crystals with better physical properties were obtained.

Metal complexes of substituted Gable porphyrins as oxidation catalysts

DOEpatents

Lyons, J.E.; Ellis, P.E. Jr.; Wagner, R.W.

1996-01-02

Transition metal complexes of Gable porphyrins are disclosed having two porphyrin rings connected through a linking group, and having on the porphyrin rings electron-withdrawing groups, such as halogen, nitro or cyano. These complexes are useful as catalysts for the oxidation of organic compounds, e.g. alkanes.

Photochemical Synthesis of Complex Carbazoles: Evaluation of Electronic Effects in Both UV- and Visible-Light Methods in Continuous Flow.

PubMed

Hernandez-Perez, Augusto C; Caron, Antoine; Collins, Shawn K

2015-11-09

An evaluation of both a visible-light- and UV-light-mediated synthesis of carbazoles from various triarylamines with differing electronic properties under continuous-flow conditions has been conducted. In general, triarylamines bearing electron-rich groups tend to produce higher yields than triarylamines possessing electron-withdrawing groups. The incorporation of nitrogen-based heterocycles, as well as halogen-containing arenes in carbazole skeletons, was well tolerated, and often synthetically useful complementarity was observed between the UV-light and visible-light (photoredox) methods. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of novel disulfide and sulfone hybrid scaffolds as potent β-glucuronidase inhibitor.

PubMed

Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Wadood, Abdul; Rahim, Fazal; Al Muqarrabin, Laode Muhammad Ramadhan; Zaki, Hamizah Mohd; Ahmat, Norizan; Nasir, Abdul; Khan, Fahad

2016-10-01

Novel series of disulfide and sulfone hybrid analogs (1-20) were synthesized and characterized through EI-MS and (1)H NMR and evaluated for β-glucuronidase inhibitory potential. All synthesized analogs except 13 and 15 showed excellent β-glucuronidase inhibitory potential with IC50 value ranging in between 2.20-88.16μM as compared to standard d-saccharic acid 1,4 lactone (48.4±1.25μM). Analogs 19, 16, 4, 1, 17, 6, 10, 3, 18, 2, 11, 14 and 5 showed many fold potent activity against β-glucuronidase inhibitor. Structure activity relationship showed that substitution of electron withdrawing groups at ortho as well as para position on phenyl ring increase potency. Electron withdrawing groups at meta position on phenyl ring showed slightly low potency as compared to ortho and para position. The binding interactions were confirmed through molecular docking studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Design of aromatic-containing cell-penetrating peptide mimics with structurally modified π electronics.

PubMed

deRonde, Brittany M; Birke, Alexander; Tew, Gregory N

2015-02-09

Cell-penetrating peptides (CPPs) and their synthetic mimics (CPPMs) represent a class of molecules that facilitate the intracellular delivery of various cargo. Previous studies indicated that the presence of aromatic functionalities improved CPPM activity. Given that aromatic functionalities play prominent roles in membrane biology and participate in various π interactions, we explored whether these interactions could be optimized for improved CPPM activity. CPPMs were synthesized by ring-opening metathesis polymerization by using monomers that contained aromatic rings substituted with electron-donating and electron-withdrawing groups and covered an electrostatic potential range from -29.69 to +15.57 kcal mol(-1) . These groups altered the quadrupole moments of the aromatic systems and were used to test if such structural modifications changed CPPM activity. CPPMs were added to dye-loaded vesicles and the release of carboxyfluorescein was monitored as a function of polymer concentration. Changes in the effective polymer concentration to release 50% of the dye (effective concentration, EC50 ) were monitored. Results from this assay showed that the strength of the electron-donating and electron-withdrawing groups incorporated in the CPPMs did not alter polymer EC50 values or activity. This suggests that other design parameters may have a stronger impact on CPPM activity. In addition, these results indicate that a wide range of aromatic groups can be incorporated without negatively impacting polymer activity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study.

PubMed

Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Helaly, Ahmed N

2014-01-01

This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse.

Molecular Engineering Strategy for High Efficiency Fullerene-Free Organic Solar Cells Using Conjugated 1,8-Naphthalimide and Fluorenone Building Blocks.

PubMed

Do, Thu Trang; Pham, Hong Duc; Manzhos, Sergei; Bell, John M; Sonar, Prashant

2017-05-24

We designed, synthesized, and characterized a series of novel electron deficient small molecule nonfullerene acceptors based on 1,8-naphthalimide (NAI) and 9-fluorenone (FN) with different branched alkyl chains using various techniques. These molecules are based on an acceptor-donor-acceptor-donor-acceptor (A1-D-A2-D-A1) molecular design configuration with NAI as the end-capping acceptor (A1), FN as electron-withdrawing central (A2) group, and thiophene ring as a donor (D) unit. These materials are named as NAI-FN-NAI (BO) and NAI-FN-NAI (HD) where BO and HD represent butyloctyl and hexyldecyl alkyl groups, respectively. To further modify energy levels of these materials, we converted the weak electron withdrawing ketonic group (C═O) attached to the FN moiety of NAI-FN-NAI (BO) to a stronger electron withdrawing cyano group (C≡N) to obtain the compound NAI-FCN-NAI (BO) by keeping the same alkyl chain. The optical, electrochemical, and thermal properties of the new acceptors were studied. The materials exhibited higher to medium band gaps, low lowest unoccupied molecular orbital (LUMO) energy levels, and highly thermally stable properties. Organic solar cell devices employing conventional poly(3-hexylthiophene) (P3HT) a donor polymer and the newly designed small molecules as the acceptor were investigated. Among all new materials, organic solar cell devices based on NAI-FN-NAI (BO) as an acceptor exhibit the highest performance with an open circuit voltage (V OC ) of 0.88 V, a short-circuit current density (J SC ) of 9.1 mAcm -2 , a fill factor (FF) of 45%, and an overall power conversion efficiency (PCE) of 3.6%. This is the first report of 9-fluorenone based nonfullerene acceptor with P3HT donor in organic solar cell devices with such a promising performance.

The electronic-cigarette: effects on desire to smoke, withdrawal symptoms and cognition.

PubMed

Dawkins, Lynne; Turner, John; Hasna, Surrayyah; Soar, Kirstie

2012-08-01

Electronic cigarettes (e-cigarettes) are battery operated devices that deliver nicotine via inhaled vapour. Few studies have evaluated acute effects on craving and mood, and none have explored effects on cognition. This study aimed to explore the effects of the White Super e-cigarette on desire to smoke, nicotine withdrawal symptoms, attention and working memory. Eighty-six smokers were randomly allocated to either: 18 mg nicotine e-cigarette (nicotine), 0mg e-cigarette (placebo), or just hold the e-cigarette (just hold) conditions. Participants rated their desire to smoke and withdrawal symptoms at baseline (T1), and five (T2) and twenty (T3) minutes after using the e-cigarette ad libitum for 5 min. A subset of participants completed the Letter Cancellation and Brown-Peterson Working Memory Tasks. After 20 min, compared with the just hold group, desire to smoke and some aspects of nicotine withdrawal were significantly reduced in the nicotine and placebo group; the nicotine e-cigarette was superior to placebo in males but not in females. The nicotine e-cigarette also improved working memory performance compared with placebo at the longer interference intervals. There was no effect of nicotine on Letter Cancellation performance. To conclude, the White Super e-cigarette alleviated desire to smoke and withdrawal symptoms 20 min after use although the nicotine content was more important for males. This study also demonstrated for the first time that the nicotine e-cigarette can enhance working memory performance. Further evaluation of the cognitive effects of the e-cigarette and its efficacy as a cessation tool is merited. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antimalarial Activity of C-10 Substituted Triazolyl Artemisinin.

PubMed

Park, Gab-Man; Park, Hyun; Oh, Sangtae; Lee, Seokjoon

2017-12-01

We synthesized C-10 substituted triazolyl artemisinins by the Huisgen cycloaddition reaction between dihydroartemisinins (2) and variously substituted 1, 2, 3-triazoles (8a-8h). The antimalarial activities of 32 novel artemisinin derivatives were screened against a chloroquine-resistant parasite. Among them, triazolyl artemisinins with electron-withdrawing groups showed stronger antimalarial activities than those shown by the derivatives having electron-donating groups. In particularly, m-chlorotriazolyl artemisinin (9d-12d) showed antimalarial activity equivalent to that of artemisinin and could be a strong drug candidate.

Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an Electronic von Frey Apparatus

PubMed Central

Martinov, Tijana; Mack, Madison; Sykes, Akilah; Chatterjea, Devavani

2013-01-01

Measuring inflammation-induced changes in thresholds of hind paw withdrawal from mechanical pressure is a useful technique to assess changes in pain perception in rodents. Withdrawal thresholds can be measured first at baseline and then following drug, venom, injury, allergen, or otherwise evoked inflammation by applying an accurate force on very specific areas of the skin. An electronic von Frey apparatus allows precise assessment of mouse hind paw withdrawal thresholds that are not limited by the available filament sizes in contrast to classical von Frey measurements. The ease and rapidity of measurements allow for incorporation of assessment of tactile sensitivity outcomes in diverse models of rapid-onset inflammatory and neuropathic pain as multiple measurements can be taken within a short time period. Experimental measurements for individual rodent subjects can be internally controlled against individual baseline responses and exclusion criteria easily established to standardize baseline responses within and across experimental groups. Thus, measurements using an electronic von Frey apparatus represent a useful modification of the well-established classical von Frey filament-based assays for rodent mechanical allodynia that may also be applied to other nonhuman mammalian models. PMID:24378519

The unexpected roles of σ and π orbitals in electron donor and acceptor group effects on the 13C NMR chemical shifts in substituted benzenes† †Electronic supplementary information (ESI) available: Experimental 13C NMR chemical shifts, individual components of the 13C NMR shielding tensor, lists and graphics of NLMO contributions, and tables of NLMO properties. See DOI: 10.1039/c7sc02163a Click here for additional data file.

PubMed Central

Viesser, Renan V.

2017-01-01

Effects of electron-donating (R = NH2) and electron-withdrawing (R = NO2) groups on 13C NMR chemical shifts in R-substituted benzene are investigated by molecular orbital analyses. The 13C shift substituent effect in ortho, meta, and para position is determined by the σ bonding orbitals in the aryl ring. The π orbitals do not explain the substituent effects in the NMR spectrum as conventionally suggested in textbooks. The familiar electron donating and withdrawing effects on the π system by NH2 and NO2 substituents induce changes in the σ orbital framework, and the 13C chemical shifts follow the trends induced in the σ orbitals. There is an implicit dependence of the σ orbital NMR shift contributions on the π framework, via unoccupied π* orbitals, due to the fact that the nuclear shielding is a response property. PMID:28989684

A Short-Term, Multicenter, Placebo-Controlled, Randomized Withdrawal Study of a Metabotropic Glutamate 2/3 Receptor Agonist Using an Electronic Patient-Reported Outcome Device in Patients With Schizophrenia

PubMed Central

Stauffer, Virginia L.; Baygani, Simin K.; Kinon, Bruce J.; Krikke-Workel, Judith O.

2014-01-01

Abstract This 6-week, multicenter, randomized withdrawal, placebo-controlled trial sought to determine whether symptoms of physical dependence occur after abrupt cessation of pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate 2/3 receptor agonist, in patients with schizophrenia. Eligible outpatients, 18 to 65 years old who required a modification or initiation of antipsychotic medication received 4 weeks of pomaglumetad methionil during open-label treatment and then were randomized, double-blind, to continue pomaglumetad methionil or receive placebo for 2 weeks. The primary outcome compared results of the 3-day moving mean of the total score on the Discontinuation Symptom Checklist-Modified Rickels for pomaglumetad methionil-treated patients with those on placebo during the randomized withdrawal phase. An electronic patient-reported outcome (ePRO) device was used daily to record these results. During the withdrawal phase, 103 patients were randomized, and 98 patients completed the trial. There was no statistically significant evidence of withdrawal symptoms associated with placebo compared with pomaglumetad methionil continuation as measured by Discontinuation Symptom Checklist-Modified Rickels (P = 0.170). The results are supported by secondary analyses with the clinician-rated, Clinical Institute Withdrawal Assessment of Alcohol Scale Revised, which showed no statistically significant differences between treatment groups. Using the ePRO device, 82.5% of the patients achieved 75% to 100% of compliance. No discontinuations due to worsening of schizophrenia, serious adverse events, deaths, or seizures were reported during either phase of the study. These findings suggest that there is no evidence of withdrawal symptoms associated with the abrupt discontinuation of pomaglumetad methionil and that an ePRO device can be successfully used in a multicenter schizophrenia trial. PMID:25006819

Balancing the Hydrogen Evolution Reaction, Surface Energetics, and Stability of Metallic MoS 2 Nanosheets via Covalent Functionalization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, Eric E.; Zhang, Hanyu; Schuman, Samuel A.

We modify the fundamental electronic properties of metallic (1T phase) nanosheets of molybdenum disulfide (MoS 2) through covalent chemical functionalization, and thereby directly influence the kinetics of the hydrogen evolution reaction (HER), surface energetics, and stability. Chemically exfoliated, metallic MoS 2 nanosheets are functionalized with organic phenyl rings containing electron donating or withdrawing groups. We find that MoS 2 functionalized with the most electron donating functional group (p-(CH 3CH 2) 2NPh-MoS 2) is the most efficient catalyst for HER in this series, with initial activity that is slightly worse compared to the pristine metallic phase of MoS 2. The p-(CHmore » 3CH 2) 2NPh-MoS 2 is more stable than unfunctionalized metallic MoS 2 and outperforms unfunctionalized metallic MoS 2 for continuous H 2 evolution within 10 min under the same conditions. With regards to the entire studied series, the overpotential and Tafel slope for catalytic HER are both directly correlated with the electron donating strength of the functional group. The results are consistent with a mechanism involving ground-state electron donation or withdrawal to/from the MoS 2 nanosheets, which modifies the electron transfer kinetics and catalytic activity of the MoS 2 nanosheet. The functional groups preserve the metallic nature of the MoS 2 nanosheets, inhibiting conversion to the thermodynamically stable semiconducting state (2H) when mildly annealed in a nitrogen atmosphere. We propose that the electron density and, therefore, reactivity of the MoS 2 nanosheets are controlled by the attached functional groups. Functionalizing nanosheets of MoS 2 and other transition metal dichalcogenides provides a synthetic chemical route for controlling the electronic properties and stability within the traditionally thermally unstable metallic state.« less

Balancing the Hydrogen Evolution Reaction, Surface Energetics, and Stability of Metallic MoS 2 Nanosheets via Covalent Functionalization

DOE PAGES

Benson, Eric E.; Zhang, Hanyu; Schuman, Samuel A.; ...

2017-12-27

We modify the fundamental electronic properties of metallic (1T phase) nanosheets of molybdenum disulfide (MoS 2) through covalent chemical functionalization, and thereby directly influence the kinetics of the hydrogen evolution reaction (HER), surface energetics, and stability. Chemically exfoliated, metallic MoS 2 nanosheets are functionalized with organic phenyl rings containing electron donating or withdrawing groups. We find that MoS 2 functionalized with the most electron donating functional group (p-(CH 3CH 2) 2NPh-MoS 2) is the most efficient catalyst for HER in this series, with initial activity that is slightly worse compared to the pristine metallic phase of MoS 2. The p-(CHmore » 3CH 2) 2NPh-MoS 2 is more stable than unfunctionalized metallic MoS 2 and outperforms unfunctionalized metallic MoS 2 for continuous H 2 evolution within 10 min under the same conditions. With regards to the entire studied series, the overpotential and Tafel slope for catalytic HER are both directly correlated with the electron donating strength of the functional group. The results are consistent with a mechanism involving ground-state electron donation or withdrawal to/from the MoS 2 nanosheets, which modifies the electron transfer kinetics and catalytic activity of the MoS 2 nanosheet. The functional groups preserve the metallic nature of the MoS 2 nanosheets, inhibiting conversion to the thermodynamically stable semiconducting state (2H) when mildly annealed in a nitrogen atmosphere. We propose that the electron density and, therefore, reactivity of the MoS 2 nanosheets are controlled by the attached functional groups. Functionalizing nanosheets of MoS 2 and other transition metal dichalcogenides provides a synthetic chemical route for controlling the electronic properties and stability within the traditionally thermally unstable metallic state.« less

Molecular glasses of azobenzene for holographic data storage applications

NASA Astrophysics Data System (ADS)

Zarins, Elmars; Balodis, Karlis; Ruduss, Armands; Kokars, Valdis; Ozols, Andris; Augustovs, Peteris; Saharovs, Dmitrijs

2018-05-01

A series of D-N=N-A type molecular glasses where the electron acceptor part (A) contains several electron withdrawing substituents, but the electron donating part (D) of the glassy azochromophores contains amorphous phase promoting non-conjugated bulky triphenyl or hydroxyl groups have been synthesized and investigated. Results showed that the azodye physical properties depend not only on the incorporated electron withdrawing substituents but are also influenced by the bonding type of covalently attached bulky moieties. Synthesized glassy azocompounds showed glass transition temperatures up to 106 °C and thermal stability up to 312 °C. The ability to form holographic gratings in spin-cast thin films of the glassy azodyes was investigated using 532 nm and 633 nm lasers obtaining diffraction efficiency up to 57%, self-diffraction efficiency up to 15% and photosensitivity as high as 3.7 J/(cm2%). Surface relief grating (SRG) depths reached 1.1 μm and in some cases even exceeded the thickness of the films.

Quantitative study of interactions between oxygen lone pair and aromatic rings: substituent effect and the importance of closeness of contact.

PubMed

Gung, Benjamin W; Zou, Yan; Xu, Zhigang; Amicangelo, Jay C; Irwin, Daniel G; Ma, Shengqian; Zhou, Hong-Cai

2008-01-18

Current models describe aromatic rings as polar groups based on the fact that benzene and hexafluorobenzene are known to have large and permanent quadrupole moments. This report describes a quantitative study of the interactions between oxygen lone pair and aromatic rings. We found that even electron-rich aromatic rings and oxygen lone pairs exhibit attractive interactions. Free energies of interactions are determined using the triptycene scaffold and the equilibrium constants were determined by low-temperature 1H NMR spectroscopy. An X-ray structure analysis for one of the model compounds confirms the close proximity between the oxygen and the center of the aromatic ring. Theoretical calculations at the MP2/aug-cc-pVTZ level corroborate the experimental results. The origin of attractive interactions was explored by using aromatic rings with a wide range of substituents. The interactions between an oxygen lone pair and an aromatic ring are attractive at van der Waals' distance even with electron-donating substituents. Electron-withdrawing groups increase the strength of the attractive interactions. The results from this study can be only partly rationalized by using the current models of aromatic system. Electrostatic-based models are consistent with the fact that stronger electron-withdrawing groups lead to stronger attractions, but fail to predict or rationalize the fact that weak attractions even exist between electron-rich arenes and oxygen lone pairs. The conclusion from this study is that aromatic rings cannot be treated as a simple quadrupolar functional group at van der Waals' distance. Dispersion forces and local dipole should also be considered.

Controlling the Conformational Energy of a Phenyl Group by Tuning the Strength of a Nonclassical CH···O Hydrogen Bond: The Case of 5-Phenyl-1,3-dioxane.

PubMed

Bailey, William F; Lambert, Kyle M; Stempel, Zachary D; Wiberg, Kenneth B; Mercado, Brandon Q

2016-12-16

Anancomeric 5-phenyl-1,3-dioxanes provide a unique opportunity to study factors that control conformation. Whereas one might expect an axial phenyl group at C(5) of 1,3-dioxane to adopt a conformation similar to that in axial phenylcyclohexane, a series of studies including X-ray crystallography, NOE measurements, and DFT calculations demonstrate that the phenyl prefers to lie over the dioxane ring in order to position an ortho-hydrogen to participate in a stabilizing, nonclassical CH···O hydrogen bond with a ring oxygen of the dioxane. Acid-catalyzed equilibration of a series of anancomeric 2-tert-butyl-5-aryl-1,3-dioxane isomers demonstrates that remote substituents on the phenyl ring affect the conformational energy of a 5-aryl-1,3-dioxane: electron-withdrawing substituents decrease the conformational energy of the aryl group, while electron-donating substituents increase the conformational energy of the group. This effect is correlated in a very linear way to Hammett substituent parameters. In short, the strength of the CH···O hydrogen bond may be tuned in a predictable way in response to the electron-withdrawing or electron-donating ability of substituents positioned remotely on the aryl ring. This effect may be profound: a 3,5-bis-CF 3 phenyl group at C(5) in 1,3-dioxane displays a pronounced preference for the axial orientation. The results are relevant to broader conformational issues involving heterocyclic systems bearing aryl substituents.

[An examination of the determinants of social withdrawal and affinity for social withdrawal].

PubMed

Watanabe, Asami; Matsui, Yutaka; Takatsuka, Yusuke

2010-12-01

This study examined the determinants of social withdrawal using data from a survey by the Tokyo Metropolitan Government Office for Youth Affairs and Public Safety (2008). In addition, this study identified young people who showed an affinity for social withdrawal although they were not in a state of withdrawal, and examined the determinants of an affinity for social withdrawal. The results of stepwise discriminant analysis showed that factors such as social phobia, depression, violence, and emotional bonds with family differentiated between the general youth group and the social withdrawal group and the "affinity group". Social phobia, violence, and refusal to be interfered in self-decision making differentiated between the social withdrawal group and the "affinity group". This study shows that an "affinity group" should be cared as well as an actual withdrawal group.

77 FR 65937 - Advisory Council to the Internal Revenue Service; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-31

... Continuing to Balance Compliance and Tax Enforcement, Streamling the Audit Process, Managing Knowledge in the Issue Practice Groups and International Practice Networks, How Lien Withdrawal Processing should be made...) (Form 1040), Increase BMF Electronic Filing, Guidance Respecting Obligations of Tax Practitioner Under...

Correlation of Calculated Halonium Ion Structures with Experimental Product Distributions from Terminal Alkenes: The Effect of Electron-Withdrawing Fluorine Substituents on the Structure and Charge Localization of Halonium Ions (PREPRINT)

DTIC Science & Technology

2006-04-03

2) Substituting a vinyl hydrogen with a fluorine presents an interesting situation for electrophilic reactions. The π-bond is less...reactive toward electrophiles due to the electron-withdrawing effect of the vinyl fluorine . Therefore, carbocations or radical cations are destabilized...NUMBER Distributions from Terminal Alkenes: The Effect of Electron-Withdrawing Fluorine Substituents on the Structure and Charge Localization of

Interactions of p-Nitrobenzene Diazonium Fluoroborate and Analogs with the Active Sites of Acetylcholine-Receptor and -Esterase*

PubMed Central

Mautner, Henry G.; Bartels, Eva

1970-01-01

p-Nitrobenzene diazonium fluoroborate (NDF) is a potent inhibitor of the carbamylcholine-induced depolarization of the electroplax and of acetylcholinesterase. It probably forms covalent bonds with the acetylcholine-receptor and -esterase at the active site of the proteins. Its inhibitory strength is at least the same as that of trimethylammonium diazonium fluoroborate (TDF). The p-acetoxy analog, with its weaker electron-withdrawing group, is about ten times weaker as an inhibitor than the trimethylammonium or p-nitro analogs, both of which have strong electron-withdrawing groups. After treatment of the electroplax preparation with dithiothreitol, NDF remains an irreversible receptor-inhibitor, while TDF becomes a potent reversible receptor-activator. TDF is self-inhibitory: applied before reduction, it no longer depolarizes. Although the first observations on TDF suggested that the compound labels both proteins by virtue of the steric complementary of its trimethylammonium group to a negative subsite in the proteins, the present study indicates that it is the positively charged diazonium group that reacts with the active sites of the proteins to form a covalent bond with an appropriate amino-acid residue. PMID:5272331

Picolinoxy group, a new leaving group for anti SN2' selective allylic substitution with aryl anions based on Grignard reagents.

PubMed

Kiyotsuka, Yohei; Acharya, Hukum P; Katayama, Yuji; Hyodo, Tomonori; Kobayashi, Yuichi

2008-05-01

The picolinoxy group was found to be an extremely powerful leaving group for allylic substitution with aryl nucleophiles derived from ArMgBr and CuBr*Me2S. The substitution proceeds with anti SN2' pathway and with high chirality transfer. The electron-withdrawing effect of the pyridyl group and chelation to MgBr2 are likely the origin of success. Results suggesting these effects were obtained.

Different Effect of the Additional Electron-Withdrawing Cyano Group in Different Conjugation Bridge: The Adjusted Molecular Energy Levels and Largely Improved Photovoltaic Performance.

PubMed

Li, Huiyang; Fang, Manman; Hou, Yingqin; Tang, Runli; Yang, Yizhou; Zhong, Cheng; Li, Qianqian; Li, Zhen

2016-05-18

Four organic sensitizers (LI-68-LI-71) bearing various conjugated bridges were designed and synthesized, in which the only difference between LI-68 and LI-69 (or LI-70 and LI-71) was the absence/presence of the CN group as the auxiliary electron acceptor. Interestingly, compared to the reference dye of LI-68, LI-69 bearing the additional CN group exhibited the bad performance with the decreased Jsc and Voc values. However, once one thiophene moiety near the anchor group was replaced by pyrrole with the electron-rich property, the resultant LI-71 exhibited a photoelectric conversion efficiency increase by about 3 folds from 2.75% (LI-69) to 7.95% (LI-71), displaying the synergistic effect of the two moieties (CN and pyrrole). Computational analysis disclosed that pyrrole as the auxiliary electron donor (D') in the conjugated bridge can compensate for the lower negative charge in the electron acceptor, which was caused by the CN group as the electron trap, leading to the more efficient electron injection and better photovoltaic performance.

The effect of triiodothyronine on maturation and differentiation of oligodendrocyte progenitor cells during remyelination following induced demyelination in male albino rat.

PubMed

El-Tahry, H; Marei, H; Shams, A; El-Shahat, M; Abdelaziz, H; Abd El-Kader, M

2016-06-01

Demyelination was induced by two weeks cuprizone treatment. Rats of +ve control and triiodothyronine (T3) then received three subcutaneous injections of either saline or T3 day after day and sacrificed at the end of the third and fifth weeks. Animals in -ve control group received only standard rodent chow. After one week of cuprizone withdrawal the corpus callosum in +ve control and T3 treated rats was still demyelinated as revealed by MBP immunohistochemistry. The assay of PLP gene showed significant increase of T3 treated group compared to both the -ve control and +ve control groups. After three weeks, significant improvement in myelination was detected in T3-treated group compared to +ve control as detected by both MBP immunohistochemistry and electron microscopy. After one week of cuprizone withdrawal, PDGFRα positive cells and gene expression showed significant increase in +ve control and T3-treated groups as compared to -ve control with insignificant difference in between the former two groups. After three weeks of cuprizone withdrawal, PDGFRα positive cells in T3-treated and +ve control groups decreased to the control levels. These results suggest that T3 was effective in improving remyelination when administered during acute phase and might direct progenitor lineage toward oligodendrocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthetic substrates for enzyme analysis

DOEpatents

Bissell, E.R.; Mitchell, A.R.; Pearson, K.W.; Smith, R.E.

1983-06-14

Synthetic substrates are provided which may be represented as A-D. The A moiety includes an amino acid, polypeptide, or derivative. The D moiety includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons. No Drawings

Synthetic substrates for enzyme analysis

DOEpatents

Bissell, Eugene R.; Mitchell, Alexander R.; Pearson, Karen W.; Smith, Robert E.

1983-01-01

Synthetic substrates are provided which may be represented as A-D. The A moiety thereof includes an amino acid, polypeptide, or derivative thereof. The D moiety thereof includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons.

Conversion and origin of normal and abnormal temperature dependences of kinetic isotope effect in hydride transfer reactions.

PubMed

Zhu, Xiao-Qing; Li, Xiu-Tao; Han, Su-Hui; Mei, Lian-Rui

2012-05-18

The effects of substituents on the temperature dependences of kinetic isotope effect (KIE) for the reactions of the hydride transfer from the substituted 5-methyl-6-phenyl-5,6-dihydrophenanthridine (G-PDH) to thioxanthylium (TX(+)) in acetonitrile were examined, and the results show that the temperature dependences of KIE for the hydride transfer reactions can be converted by adjusting the nature of the substituents in the molecule of the hydride donor. In general, electron-withdrawing groups can make the KIE to have normal temperature dependence, but electron-donating groups can make the KIE to have abnormal temperature dependence. Thermodynamic analysis on the possible pathways of the hydride transfer from G-PDH to TX(+) in acetonitrile suggests that the transfers of the hydride anion in the reactions are all carried out by the concerted one-step mechanism whether the substituent is an electron-withdrawing group or an electron-donating group. But the examination of Hammett-type free energy analysis on the hydride transfer reactions supports that the concerted one-step hydride transfer is not due to an elementary chemical reaction. The experimental values of KIE at different temperatures for the hydride transfer reactions were modeled by using a kinetic equation formed according to a multistage mechanism of the hydride transfer including a returnable charge-transfer complex as the reaction intermediate; the real mechanism of the hydride transfer and the root that why the temperature dependences of KIE can be converted as the nature of the substituents are changed were discovered.

Dual Functioning Thieno-Pyrrole Fused BODIPY Dyes for NIR Optical Imaging and Photodynamic Therapy: Singlet Oxygen Generation without Heavy Halogen Atom Assistance.

PubMed

Watley, Ryan L; Awuah, Samuel G; Bio, Moses; Cantu, Robert; Gobeze, Habtom B; Nesterov, Vladimir N; Das, Sushanta K; D'Souza, Francis; You, Youngjae

2015-06-01

We discovered a rare phenomenon wherein a thieno-pyrrole fused BODIPY dye (SBDPiR690) generates singlet oxygen without heavy halogen atom substituents. SBDPiR690 generates both singlet oxygen and fluorescence. To our knowledge, this is the first example of such a finding. To establish a structure-photophysical property relationship, we prepared SBDPiR analogs with electron-withdrawing groups at the para-position of the phenyl groups. The electron-withdrawing groups increased the HOMO-LUMO energy gap and singlet oxygen generation. Among the analogs, SBDPiR688, a CF3 analog, had an excellent dual functionality of brightness (82290 m(-1)  cm(-1) ) and phototoxic power (99170 m(-1)  cm(-1) ) comparable to those of Pc 4, due to a high extinction coefficient (211 000 m(-1)  cm(-1) ) and balanced decay (Φflu =0.39 and ΦΔ =0.47). The dual functionality of the lead compound SBDPiR690 was successfully applied to preclinical optical imaging and for PDT to effectively control a subcutaneous tumor. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effects of e-cigarette visual appearance on craving and withdrawal symptoms in abstinent smokers.

PubMed

Dawkins, Lynne; Munafò, Marcus; Christoforou, Gina; Olumegbon, Naomi; Soar, Kirstie

2016-02-01

Electronic cigarette (e-cigarette) use is becoming increasing popular among smokers, and there is a plethora of devices available. Nicotine delivery is clearly important for reducing tobacco craving and withdrawal symptoms, but other sensorimotor aspects of e-cigarettes (such as visual appearance) may contribute to this effect. This study explored whether it is important for an e-cigarette to visually resemble a tobacco cigarette in order to reduce craving and withdrawal symptoms. Sixty-three cigarette smokers (40% female, aged 18-65 years) who were not current e-cigarette users were randomly allocated to take ten 3-s puffs from either a white or a red first-generation e-cigarette following overnight abstinence. Current craving (urge to smoke) and nicotine withdrawal symptoms (using the Mood and Physical Symptoms Scale [MPSS]) were measured before and 10 min after use. Linear regression revealed higher craving and withdrawal symptoms in the red condition versus the white condition, but only among those who were e-cigarette naive (craving: B = .76, p = .009; withdrawal symptoms: B = 2.18, p = .009), not among those with e-cigarette experience (craving: B = -.08, p = .89; withdrawal symptoms: B = .24, p = .81), and these effects differed between groups (p = .04 and 0.01 for craving and withdrawal symptoms, respectively). In conclusion, cigarette-like appearance was associated with lower craving and withdrawal symptoms, but only for those with no prior e-cigarette experience. This effect, putatively mediated via classical conditioning or expectancies, may aid understanding of smokers' initial preferences for "cigalike" e-cigarette devices. (c) 2016 APA, all rights reserved).

The Influence of the Anionic Counter-Ion on the Activity of Ammonium Substituted Hoveyda-Type Olefin Metathesis Catalysts in Aqueous Media

NASA Astrophysics Data System (ADS)

Gułajski, Łukasz; Grela, Karol

Polar olefin metathesis catalysts, bearing an ammonium group are presented. The electron withdrawing ammonium group not only activates the catalysts electronically, but at the same time makes the catalysts more hydrophilic. Catalysts can be therefore efficiently used not only in traditional media, such as methylene chloride and toluene, but also in technical-grade alcohols, alcohol— water mixtures and in neat water. Finally, in this overview the influence of the anionic counter-ion on the activity of ammonium substituted Hoveyda-type olefin metathesis catalysts in aqueous media is presented.

TRANSFORMATION OF NITROSOBENZENES AND HYDROXYLANILINES BY FE II SPECIES: ELUCIDATION OF MECHANISM, EFFECT OF FERRIC OXIDES AND PH

EPA Science Inventory

Nitrosobenzenes, the first intermediates in the reduction of nitrobenzenes, were reduced by Fe(II) solutions as well as by Fe(II)-treated goethite suspensions (Fe(II)/G). Results indicate a reactivity trend in which electron-withdrawing groups in the para position increased the ...

Reactivity measurement in estimation of benzoquinone and benzoquinone derivatives’ allergenicity

PubMed Central

Mbiya, Wilbes; Chipinda, Itai; Simoyi, Reuben H.; Siegel, Paul D.

2015-01-01

Benzoquinone (BQ) and benzoquinone derivatives (BQD) are used in the production of dyes and cosmetics. While BQ, an extreme skin sensitizer, is an electrophile known to covalently modify proteins via Michael Addition (MA) reaction whilst halogen substituted BQD undergo nucleophilic vinylic substitution (SNV) mechanism onto amine and thiol moieties on proteins, the allergenic effects of adding substituents on BQ have not been reported. The effects of inserting substituents on the BQ ring has not been studied in animal assays. However, mandated reduction/elimination of animals used in cosmetics testing in Europe has led to an increased need for alternatives for the prediction of skin sensitization potential. Electron withdrawing and electron donating substituents on BQ were assessed for effects on BQ reactivity toward nitrobenzene thiol (NBT). The NBT binding studies demonstrated that addition of EWG to BQ as exemplified by the chlorine substituted BQDs increased reactivity while addition of EDG as in the methyl substituted BQDs reduced reactivity. BQ and BQD skin allerginicity was evaluated in the murine local lymph node assay (LLNA). BQD with electron withdrawing groups had the highest chemical potency followed by unsubstituted BQ and the least potent were the BQD with electron donating groups. The BQD results demonstrate the impact of inductive effects on both BQ reactivity and allergenicity, and suggest the potential utility of chemical reactivity data for electrophilic allergen identification and potency ranking. PMID:26612505

Effects of Acute Withdrawal on Ethanol-Induced Conditioned Place Preference in DBA/2J mice

PubMed Central

Dreumont, Sarah E.; Cunningham, Christopher L.

2013-01-01

Rationale Re-exposure to ethanol during acute withdrawal might facilitate the transition to alcoholism by enhancing the rewarding effect of ethanol. Objective The conditioned place preference (CPP) procedure was used to test whether ethanol reward is enhanced during acute withdrawal. Methods DBA/2J mice were exposed to an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0 or 1.5 g/kg IP) was paired with a distinctive floor cue (CS+), whereas saline was paired with a different floor cue (CS−). The Withdrawal (W) group received CS+ trials during acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before each trial. The No Withdrawal (NW) group did not experience acute withdrawal during conditioning trials, but was matched for acute withdrawal experience. Floor preference was tested in the absence of ethanol or acute withdrawal. Results All groups eventually showed a dose-dependent preference for the ethanol-paired cue, but development of CPP was generally more rapid and stable in the W groups than in the NW groups. Acute withdrawal suppressed the normal activating effect of ethanol during CS+ trials, but there were no group differences in test activity. Conclusions Acute withdrawal enhanced ethanol’s rewarding effect as indexed by CPP. Since this effect depended on ethanol exposure during acute withdrawal, the enhancement of ethanol reward was likely mediated by the alleviation of acute withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during acute withdrawal may be a key component in the shift from episodic to chronic ethanol consumption that characterizes alcoholism. PMID:24096534

Elucidating the Structure-Reactivity Correlations of Phenothiazine-Based Fluorescent Probes toward ClO.

PubMed

Wang, Shichao; Zhang, Boyu; Wang, Wenjing; Feng, Gang; Yuan, Daqiang; Zhang, Xuanjun

2018-06-07

In this work, with the aim of developing effective molecular probes and investigating the structure-reactivity correlation, a short series of phenothiazine-based fluorescent probes are designed for the detection of ClO - with differing electron push-pull groups. Sensing experiment results and single-crystal X-ray analysis with the aid of time-dependent DFT (TD-DFT) calculations reveal that substituting groups with increasing electron-withdrawing ability can increase the dihedral angle of the phenothiazine moiety and reduce the gap energy of the probes, leading to enhanced reactivity toward ClO - . Both PT1 and PT2 show two-color switching upon detection of ClO - . PT1, with the strong electron-donating group thiophene, shows a fluorescence color switch from salmon to blue. PT2, with a medium electron-donating/accepting group benzothiazole, shows a fluorescence color switch from red to green. However, both PT1 and PT2 show almost no response to ONOO - . Through the introduction of strong electron-withdrawing ketone combined with a cyano group, PT3 shows a cyan emission upon detection of ClO - and weak red emission upon detection of ONOO - . HRMS and 1 H NMR results confirm that PT1 and PT2 have the same sensing mode, in which the divalent sulfur of phenothiazine can be oxidized to sulfoxide by ClO - . Upon reaction with ClO - , PT3 experiences two-step reactions. It is first oxidized into the sulfone structure by ClO - , and then transformed into sulfoxide phenothiazine aldehyde. Upon encountering ONOO - , PT3 changes into an aldehyde structure and some nonfluorescent byproducts. Owing to their special selectivity and high sensitivity, PT1 and PT2 are applied to image the endogenous ClO - in macrophage cells and zebrafish larvae. This study is expected to provide useful guidelines for probe design for various applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Theoretical investigation of the charge-transfer properties in different meso-linked zinc porphyrins for highly efficient dye-sensitized solar cells.

PubMed

Namuangruk, Supawadee; Sirithip, Kanokkorn; Rattanatwan, Rattanawelee; Keawin, Tinnagon; Kungwan, Nawee; Sudyodsuk, Taweesak; Promarak, Vinich; Surakhot, Yaowarat; Jungsuttiwong, Siriporn

2014-06-28

The charge transfer effect of different meso-substituted linkages on porphyrin analogue 1 (A1, B1 and C1) was theoretically investigated using density functional theory (DFT) and time-dependent DFT (TDDFT) calculations. The calculated geometry parameters and natural bond orbital analysis reveal that the twisted conformation between porphyrin macrocycle and meso-substituted linkages leads to blocking of the conjugation of the conjugated backbone, and the frontier molecular orbital plot shows that the intramolecular charge transfer of A1, B1 and C1 hardly takes place. In an attempt to improve the photoinduced intramolecular charge transfer ability of the meso-linked zinc porphyrin sensitizer, a strong electron-withdrawing group (CN) was introduced into the anchoring group of analogue 1 forming analogue 2 (A2, B2 and C2). The density difference plot of A2, B2 and C2 shows that the charge transfer properties dramatically improved. The electron injection process has been performed using TDDFT; the direct charge-transfer transition in the A2-(TiO2)38 interacting system takes place; our results strongly indicated that introducing electron-withdrawing groups into the acceptor part of porphyrin dyes can fine-tune the effective conjugation length of the π-spacer and improve intramolecular charge transfer properties, consequently inducing the electron injection process from the anchoring group of the porphyrin dye to the (TiO2)38 surface which may improve the conversion efficiency of the DSSCs. Our calculated results can provide valuable information and a promising outlook for computation-aided sensitizer design with anticipated good properties in further experimental synthesis.

Protecting Group and Solvent Control of Stereo- and Chemoselectivity in Glucal 3-Carbamate Amidoglycosylation

PubMed Central

Gupta, Ritu; Sogi, Kimberly M.; Bernard, Sarah E.; Decatur, John D.; Rojas, Christian M.

2009-01-01

In the Rh2(OAc)4-catalyzed amidoglycosylation of glucal 3-carbamates, anomeric stereoselectivity and the extent of competing C3–H oxidation depend on the 4O and 6O protecting groups. Acyclic protection permits high α-anomer selectivity with further improvement in less polar solvents, while electron-withdrawing protecting groups limit C3-oxidized byproducts. Stereocontrol and bifurcation between alkene insertion and C3–H oxidation reflect an interplay of conformational, stereoelectronic, and inductive factors. PMID:19254041

Enhancement of polyisoprene latex production

NASA Technical Reports Server (NTRS)

Bauman, Albert J. (Inventor)

1979-01-01

Production of high molecular weight polyisoprene latex is enhanced by administering to plants, particularly Guayule Plants, an amine containing at least one two-carbon chain substituent and preferably substituted trialkylamine of the general structure: ##STR1## where R.sub.4, R.sub.5 and R.sub.6 are alkyl, preferably ethyl and at least one of R.sub.4, R.sub.5 and R.sub.6 is preferably an electron withdrawing group substituted aryloxy or arylthio ethyl group.

Asymmetrical squaraines for high-performance small-molecule organic solar cells with a short circuit current of over 12 mA cm(-2).

PubMed

Chen, Yao; Zhu, Youqin; Yang, Daobin; Luo, Qian; Yang, Lin; Huang, Yan; Zhao, Suling; Lu, Zhiyun

2015-04-11

An asymmetrical squaraine dye (Py-3) with its two electron-donating aryl groups directly linked to the electron-withdrawing squaric acid core possesses an ideal bandgap of 1.33 eV, together with an intense and broad absorption band in the range 550-950 nm. Hence, the resulting solution-processed solar cells display an impressive Jsc of 12.03 mA cm(-2) and a PCE of 4.35%.

Microwave-Assisted Organocatalytic Intramolecular Knoevenagel/Hetero Diels-Alder Reaction with O-(Arylpropynyloxy)-Salicylaldehydes: Synthesis of Polycyclic Embelin Derivatives.

PubMed

Martín-Acosta, Pedro; Feresin, Gabriela; Tapia, Alejandro; Estévez-Braun, Ana

2016-10-21

A highly efficient and regioselective approach to new polycyclic embelin derivatives through a domino Knoevenagel condensation/intramolecular hetero Diels-Alder reaction using O-(arylpropynyloxy)-salicylaldehydes in the presence of ethylenediamine diacetate (EDDA) is reported. This organocatalyzed protocol is compatible toward a wide range of aryl-substituted alkynyl ethers with electron-donating and electron-withdrawing groups. When other active methylene compounds were subjected to this domino reaction the corresponding adducts were obtained in high yield.

Substituent effects in infrared spectroscopy—VII. Meta and para substituted methanesulphonanilides

NASA Astrophysics Data System (ADS)

Laurence, C.; Berthelot, M.; Lucon, M.; Tsuno, Y.

Substituent effects on the NH frequencies of the conformers of methanesulphonanilides, their cyclic dimers and their hydrogen bonded complexes with acetonitrile have been analysed by means of the Hammet equation. An electron-withdrawing substituent may either increase or decrease ν(NH) in the XC 6H 4NHY series according to the electronic nature of the Y group. This can be explained by the non-monotonic dependence of the NH stretching frequency on the ionic character of the NH bond.

A Simple Base-Mediated Halogenation of Acidic sp2 C-H Bonds under Non-Cryogenic Conditions

PubMed Central

Do, Hien-Quang; Daugulis, Olafs

2009-01-01

A new method has been developed for in situ halogenation of acidic sp2 carbon-hydrogen bonds in heterocycles and electron-deficient arenes. Either selective monohalogenation or one-step exhaustive polyhalogenation is possible for substrates possessing several C-H bonds that are flanked by electron-withdrawing groups. For the most acidic arenes, such as pentafluorobenzene, K3PO4 base can be employed instead of BuLi for metalation/halogenation sequences. PMID:19102661

Two-photon or higher-order absorbing optical materials and methods of use

NASA Technical Reports Server (NTRS)

Marder, Seth (Inventor); Perry, Joseph (Inventor)

2012-01-01

Compositions capable of simultaneous two-photon absorption and higher order absorptivities are provided. Compounds having a donor-pi-donor or acceptor-pi-acceptor structure are of particular interest, where the donor is an electron donating group, acceptor is an electron accepting group, and pi is a pi bridge linking the donor and/or acceptor groups. The pi bridge may additionally be substituted with electron donating or withdrawing groups to alter the absorptive wavelength of the structure. Also disclosed are methods of generating an excited state of such compounds through optical stimulation with light using simultaneous absorption of photons of energies individually insufficient to achieve an excited state of the compound, but capable of doing so upon simultaneous absorption of two or more such photons. Applications employing such methods are also provided, including controlled polymerization achieved through focusing of the light source(s) used.

Enhancing electron transport in molecular wires by insertion of a ferrocene center.

PubMed

Sun, Yan-Yan; Peng, Zheng-Lian; Hou, Rong; Liang, Jing-Hong; Zheng, Ju-Fang; Zhou, Xiao-Yi; Zhou, Xiao-Shun; Jin, Shan; Niu, Zhen-Jiang; Mao, Bing-Wei

2014-02-14

We have determined the conductance of alkane-linked ferrocene molecules with carboxylic acid anchoring groups using the STM break junction technique, and three sets of conductance values were found, i.e. high conductance (HC), medium conductance (MC) and low conductance (LC) values. The enhancing effect of the incorporated ferrocene on the electron transport in saturated alkane molecular wires is demonstrated by the increased conductance of the ferrocene molecules, attributed to the reduction of the tunneling barrier and the HOMO-LUMO gap induced by the insertion of ferrocene. Furthermore, the electron-withdrawing carbonyl group on the unconjugated backbone has little or no influence on single-molecule conductance. The current work provides a feasible approach for the design of high-performance molecular wires.

Application of two-dimensional binary fingerprinting methods for the design of selective Tankyrase I inhibitors.

PubMed

Muddukrishna, B S; Pai, Vasudev; Lobo, Richard; Pai, Aravinda

2017-11-22

In the present study, five important binary fingerprinting techniques were used to model novel flavones for the selective inhibition of Tankyrase I. From the fingerprints used: the fingerprint atom pairs resulted in a statistically significant 2D QSAR model using a kernel-based partial least square regression method. This model indicates that the presence of electron-donating groups positively contributes to activity, whereas the presence of electron withdrawing groups negatively contributes to activity. This model could be used to develop more potent as well as selective analogues for the inhibition of Tankyrase I. Schematic representation of 2D QSAR work flow.

/sup 13/C NMR spectra of cyclic nitrones. 2. 1- and 4-substituted 2,2,5,5-tetramethyl-3-imidazoline 3-oxides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grigor'ev, I.A.; Shchukin, G.I.; Martin, V.V.

1985-08-01

The chemical shift of the carbon atom of the nitrone group in the /sup 13/C NMR spectra of 3-imidazoline 3-oxides lies in the region of 117-152 ppm and depends on the electronic effect of the substituents at positions 1, 4, and 5 of the heterocycle. Increase in the electron-withdrawing character of the substituent at these positions leads to an upfield shift of the signal for the nitrone carbon atom, and this corresponds to the increase in electron density on it.

Successful withdrawal from high-dose benzodiazepine in a young patient through electronic monitoring of polypharmacy: a case report in an ambulatory setting.

PubMed

Loscertales, Hèctor R; Wentzky, Valerie; Dürsteler, Kenneth; Strasser, Johannes; Hersberger, Kurt E; Arnet, Isabelle

2017-05-01

Dependence on high-dose benzodiazepines (BZDs) is well known and discontinuation attempts are generally unsuccessful. A well established protocol for high-dose BZD withdrawal management is lacking. We present the case of withdrawal from high-dose lorazepam (>20 mg daily) in an unemployed 35-year-old male outpatient through agonist substitution with long-acting clonazepam and electronic monitoring over 28 weeks. All medicines were repacked into weekly 7 × 4 cavity multidose punch cards with an electronic monitoring system. The prescribed daily dosages of BZDs were translated into an optimal number of daily tablets, divided into up to four units of use. Withdrawal was achieved by individual leftover of a small quantity of BZDs that was placed in a separate compartment. Feedback with visualization of intake over the past week was given during weekly psychosocial sessions. Stepwise reduction was obtained by reducing the mg content of the cavities proportionally to the leftovers, keeping the number of cavities in order to maintain regular intake behavior, and to determine the dosage decrease. At week 28, the primary objectives were achieved, that is, lorazepam reduction to 5 mg daily and cannabis abstinence. Therapy was continued using multidrug punch cards without electronic monitoring to maintain the management system. At week 48, a smaller size weekly pill organizer with detachable daily containers was dispensed. At week 68, the patient's therapy was constant with 1.5 mg clonazepam + 5 mg lorazepam daily for anxiety symptoms and the last steps of withdrawal were started. Several key factors led to successful withdrawal from high-dose BZD in this outpatient, such as the use of weekly punch cards coupled with electronic monitoring, the patient's empowerment over the withdrawal process, and the collaboration of several healthcare professionals. The major implication for clinical care is reduction by following the leftovers, and not a diktat from the healthcare professionals.

Solvatochromic investigation of highly fluorescent 2-aminobithiophene derivatives.

PubMed

Bolduc, Andréanne; Dong, Yanmei; Guérin, Amélie; Skene, W G

2012-05-21

The solvatochromic and electrochemical properties of electronic push-pull 2-aminobithiophenes consisting of an aldehyde and nitro withdrawing groups were examined. With the use of an integrating sphere, the absolute quantum yields of the bithiophenes were measured. They were found to be highly fluorescent (Φfl > 70%), provided the nitro group was not located in the 4'-position. High fluorescence yields were observed regardless of solvent, except for alcohols, notably methanol and ethanol. Cryofluorescence was used to probe the bithiophene temperature dependent excited state deactivation modes. The singlet excited state deactivation mode other than fluorescence was found to be internal conversion involving rotation around the thiophene-thiophene bond. Deactivation by intersystem crossing to the triplet state occurred in ca. 40% only for the unsubstituted 2-aminobithiophene. In contrast, the fluorescence was quenched by photoinduced intramolecular electron transfer when the nitro group was located in the 4'-position of the bithiophene. Both the absorbance and fluorescence of the bithiophenes were found to be solvatochromic with more pronounced solvent dependent shifts being observed with the fluorescence. In fact, both the fluorescence and Stokes shifts were linearly dependent on the ET(30) solvent parameter. Deviations from the linear trend of the Stokes shift with ET(30) were observed in ethanol and methanol as a result of intermolecular hydrogen abstraction from the solvent and by the excited nitro group. The oxidation potential of the bithiophenes was also highly dependent on the type and number of the electron withdrawing substituents, with values ranging between 0.8 and 1.2 V vs. SCE.

Tracking bacterial infection of macrophages using a novel red-emission pH sensor.

PubMed

Jin, Yuguang; Tian, Yanqing; Zhang, Weiwen; Jang, Sei-Hum; Jen, Alex K-Y; Meldrum, Deirdre R

2010-10-01

The relationship between bacteria and host phagocytic cells is key to the induction of immunity. To visualize and monitor bacterial infection, we developed a novel bacterial membrane permeable pH sensor for the noninvasive monitoring of bacterial entry into murine macrophages. The pH sensor was constructed using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) as an electron-withdrawing group and aniline as an electron-donating group. A piperazine moiety was used as the pH-sensitive group. Because of the strong electron-donating and -withdrawing units conjugated in the sensing moiety M, the fluorophore emitted in the red spectral window, away from the autofluorescence regions of the bacteria. Following the engulfment of sensor-labeled bacteria by macrophages and their subsequent merger with host lysosomes, the resulting low-pH environment enhances the fluorescence intensity of the pH sensors inside the bacteria. Time-lapse analysis of the fluorescent intensity suggested significant heterogeneity of bacterial uptake among macrophages. In addition, qRT-PCR analysis of the bacterial 16 S rRNA gene expression within single macrophage cells suggested that the 16 S rRNA of the bacteria was still intact 120 min after they had been engulfed by macrophages. A toxicity assay showed that the pH sensor has no cytotoxicity towards either E. coli or murine macrophages. The sensor shows good repeatability, a long lifetime, and a fast response to pH changes, and can be used for a variety of bacteria.

Novel High Efficient Organic Photovoltaic Materials: Appendix for Summary of Research. Appendix

NASA Technical Reports Server (NTRS)

Sun, Sam

2002-01-01

There are many different kinds of conjugated polymers that may be useful in photovoltaic devices. So far, the most popular and successful conjugated polymers used in photovoltaic devices include poly(1,4-)phenylenevinylenes (PPV), C60 and their derivatives. The discovery of electro-luminescence in PPV has stimulated a great deal of interest in developing "plastic" solid-state semiconductor devices. The overall synthetic methodology for the preparation of PPV can be divided into three main categories: (1) side chain derivatization, (2) precursor approach, and (3) in-situ polymerization. In this project, the first method was adopted. As discussed in project proposal and literatures, the overall efficiency of photovoltaic devices containing conjugated polymers is determined by the materials ability to generate excitons from incoming radiation, and then to separate the charges at donor/acceptor interfaces, and then to transport charges to respective electrodes. Given that effective exciton diffusion range are typical less then 30 nm, unique morphological structures are needed. This need led to several research groups to the idea that interpenetrating or bi-continuous networks of donor (electron donating) and acceptor (electron withdrawing) polymers should give better results. One approach involved the use of functionalized PPV. The attachment of electron withdrawing cyano groups to a PPV forms the CN-PPV, making it a strong electron acceptor. Underivatized PPV is a generally considered a hole-transporting material. Using blends of MEH-PPV, a soluble donor PPV derivative, as a hole transporter and CN-PPV as an electron transporter, a quantum efficiencies of up to 6% was achieved.

Substituent and Solvent Effects on the Absorption Spectra of Cation-π Complexes of Benzene and Borazine: A Theoretical Study.

PubMed

Sarmah, Nabajit; Bhattacharyya, Pradip Kr; Bania, Kusum K

2014-05-29

Time-dependent density functional theory (TDDFT) has been used to predict the absorption spectra of cation-π complexes of benzene and borazine. Both polarized continuum model (PCM) and discrete solvation model (DSM) and a combined effect of PCM and DSM on the absorption spectra have been elucidated. With decrease in size of the cation, the π → π* transitions of benzene and borazine are found to undergo blue and red shift, respectively. A number of different substituents (both electron-withdrawing and electron-donating) and a range of solvents (nonpolar to polar) have been considered to understand the effect of substituent and solvents on the absorption spectra of the cation-π complexes of benzene and borazine. Red shift in the absorption spectra of benzene cation-π complexes are observed with both electron-donating groups (EDGs) and electron-withdrawing groups (EWGs). The same trend has not been observed in the case of substituted borazine cation-π complexes. The wavelength of the electronic transitions corresponding to cation-π complexes correlates well with the Hammet constants (σ p and σ m ). This correlation indicates that the shifting of spectral lines of the cation-π complexes on substitution is due to both resonance and inductive effect. On incorporation of solvent phases, significant red or blue shifting in the absorption spectra of the complexes has been observed. Kamlet-Taft multiparametric equation has been used to explain the effect of solvent on the absorption spectra of complexes. Polarity and polarizability are observed to play an important role in the solvatochromism of the cation-π complexes.

The spectroscopic impact of interactions with the four Gouterman orbitals from peripheral decoration of porphyrins with simple electron withdrawing and donating groups.

PubMed

Zhang, Angel; Kwan, Lydia; Stillman, Martin J

2017-11-07

Tetrapyrroles are of great interest for solar cell and photodynamic therapy applications due to their structural analogy with chlorophyll, a natural photosensitizer. Unsubstituted symmetric porphyrins exhibit weak absorption in the red region which makes them unsuitable for these applications. The push-pull peripheral decoration modifies the energies of the frontier molecular orbitals, which in turn influences the tetrapyrrole's spectroscopic properties. The absorption, magnetic circular dichroism, and emission spectra were measured for four zinc tetratolylporphyrin compounds substituted peripherally with a fused dimethoxybenzo group as an electron withdrawing group (EWG) on one pyrrole and on the opposite pyrrole, a single acetamido (1), a nitro (2), a proton (3), or a benzoylamino (4) substituent. Unusually, the magnetic circular dichroism spectrum of 2 exhibited a negative A term for the lowest energy absorption band (the Q band) and its emission spectrum was also unlike those of 1, 3, and 4. A complete computational analysis was carried out to obtain the energies and electron distribution, shown by electron density surfaces, of the four Gouterman MOs. TD-DFT calculations showed that for 2, ΔLUMO was greater than ΔHOMO, which accounted for the observed negative A term. The trend in the estimated MCD A term magnitudes, normalized to the absorbance as [A/(dipole strength) BM], provides experimental confirmation of the computationally determined ratio of ΔLUMO/ΔHOMO data. The value of ΔHOMO was confirmed by the trend in oscillator strengths. A series of fictive porphyrins (F1-F5) incorporating simple push-pull substituents were designed and their electronic structures were investigated using TD-DFT calculations. The substituents in the five fictive molecules illustrate the differential effect of the donor and acceptor groups in the β-position of the pyrroles on the relative stabilities of the four Gouterman orbitals. NO 2 groups result in the greatest splitting of the LUMO pair. We show that on using strong EWGs, opposite electron donating groups result in a ΔLUMO > 0, which red-shifts the Q band and introduces a strong dipole. With the nitro and formyl EWGs, ΔLUMO becomes greater than ΔHOMO, resulting in a complex electronic structure of the Q band, recognizable by a negative A term suggesting a design objective for future photosensitizers.

Physical origins of weak H 2 binding on carbon nanostructures: Insight from ab initio studies of chemically functionalized graphene nanoribbons

DOE PAGES

Ulman, Kanchan; Bhaumik, Debarati; Wood, Brandon C.; ...

2014-05-05

Here, we have performed ab initio density functional theory calculations, incorporating London dispersion corrections, to study the absorption of molecular hydrogen on zigzag graphene nanoribbons whose edges have been functionalized by OH, NH 2, COOH, NO 2, or H 2PO 3. We find that hydrogen molecules always preferentially bind at or near the functionalized edge, and display induced dipole moments. Binding is generally enhanced by the presence of polar functional groups. Furthermore, the largest gains are observed for groups with oxygen lone pairs that can facilitate local charge reorganization, with the biggest single enhancement in adsorption energy found for “strongmore » functionalization” by H 2PO 3 (115 meV/H 2 versus 52 meV/H 2 on bare graphene). We show that for binding on the “outer edge” near the functional group, the presence of the group can introduce appreciable contributions from Debye interactions and higher-order multipole electrostatic terms, in addition to the dominant London dispersion interactions. For those functional groups that contain the OH moiety, the adsorption energy is linearly proportional to the number of lone pairs on oxygen atoms. Mixed functionalization with two different functional groups on a graphene edge can also have a synergistic effect, particularly when electron-donating and electron-withdrawing groups are combined. For binding on the “inner edge” somewhat farther from the functional group, most of the binding again arises from London interactions; however, there is also significant charge redistribution in the π manifold, which directly reflects the electron donating or withdrawing capacity of the functional group. These results offer insight into the specific origins of weak binding of gas molecules on graphene, and suggest that edge functionalization could perhaps be used in combination with other strategies to increase the uptake of hydrogen in graphene. They also have relevance for the storage of hydrogen in porous carbon materials, such as activated carbons.« less

Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat.

PubMed

Eltony, Sohair A; Abdelhameed, Sally Y

2017-04-01

Abnormal vision has been reported by 3% of patients treated with sildenafil citrate (Viagra). Although many men use Viagra for an extended period for treatment of erectile dysfunction, the implications of the long term-daily use of it on the retina and optic nerve are unclear. To investigate the effect of chronic daily use of sildenafil citrate in a dose equivalent to men preferred therapeutic dose on the histology of the retina and optic nerve of adult male rat. Eighteen adult male Wistar rats were equally divided into three groups. Group I: control. Group II: treated with sildenafil citrate orally (10mg/kg/day) for 8 weeks. Group III (withdrawal): treated as group II and then left for 4 weeks without treatment. Specimens from the retina and optic nerve were processed for light and electron microscopy. In sildenafil citrate treated group, the retina and optic nerve revealed vacuolations and congested blood capillaries with apoptotic endothelial and pericytic cells, and thickened basal lamina. Caspase-3 (apoptotic marker) and CD31 (endothelial marker) expression increased. Glial cells revealed morphological changes: Müller cells lost their processes, activated microglia, astrocytic clasmatodendrosis, degenerated oligodendrocytes surrounded by disintegrated myelin sheathes of the optic nerve fibers. The retina and optic nerve of the withdrawal group revealed less vacuolations and congestion, and partial recovery of the glial cells. Chronic treatment with sildenafil citrate (Viagra) caused toxic effect on the structure of the retina and optic nerve of the rat. Partial recovery was observed after drug withdrawal. Copyright © 2017 Elsevier Ltd. All rights reserved.

A theoretical investigation of substituent effects on the stability and reactivity of N-heterocyclic olefin carboxylates.

PubMed

Dong, Liang; Wen, Jun; Li, Weiyi

2015-08-21

A theoretical study of substituent effects on the stability and reactivity of novel synthesized N-heterocyclic olefin (NHO) carboxylates has been performed using a combination of density functional theory (DFT) calculations, molecular electrostatic potential (MESP) minimum and nucleophilicity index analyses. These calculations demonstrate that the nucleophilicity of free NHO is stronger than that of the NHO-CO2 adduct and, hence, the thermally unstable NHO-CO2 adduct should be a more efficient organocatalyst for nucleophile-mediated reactions. The stability of the NHO-CO2 adduct, as well as the reactivity of free NHO, is strongly dependent on the electronic and steric effects of the C- and N-substituents on the imidazole ring. This dependency is reflected by the measured MESP minimum for the carboxylate moiety, the NHO-CO2 adduct (Vmin1), and the terminal carbon atom of free NHO (Vmin2). C-Substituents exert only electronic effects while N-substituents exert both electronic and steric effects. In general, the electron-withdrawing groups on the C- and N-positions favor decarboxylation while weakening the reactivity of NHO. These positions favor decarboxylation due to the simultaneous decrease of the electronic density on the carboxyl moiety of the NHO-CO2 and the terminal carbon atom of olefins. Additionally, the balance between the stability of the NHO-CO2 and the reactivity of free NHO can be tuned by the combined effects of the C- and N-substituents. The introduction of weak electron-withdrawing groups at the C-position and aromatic substituents or similar ring-strained entities at the N-position favors decarboxylation of the NHO-CO2 adduct and ensures the free NHO as a strong nucleophile.

Congested ferrocenyl polyphosphanes bearing electron-donating or electron-withdrawing phosphanyl groups: assessment of metallocene conformation from NMR spin couplings and use in palladium-catalyzed chloroarenes activation.

PubMed

Mom, Sophal; Beaupérin, Matthieu; Roy, David; Royer, Sylviane; Amardeil, Régine; Cattey, Hélène; Doucet, Henri; Hierso, J-C

2011-11-21

The synthesis of novel substituted cyclopentadienyl salts that incorporate both a congested branched alkyl group (tert-butyl, (triphenyl)methyl, or tri(4-tert-butyl)phenylmethyl) and a phosphanyl group is reported. The introduction of either electron-withdrawing or electron-donating substituents (furyl, i-propyl, cyclohexyl, tert-butyl) on P atoms was generally achieved in high yield. The modular synthesis of ferrocenyl polyphosphanes from an assembly of these cyclopentadienyl salts was investigated, leading to the formation of new triphosphanes (denoted as 9-12) and diphosphanes (denoted as 14-16). The resulting phosphanes are not sensitive to air or moisture, even when electron-rich substituents are present. This set of polyphosphanes displays varied conformational features, which are discussed in the light of their multinuclear NMR characterization in solution and of the X-ray solid state structure of the representative triphosphane 1,2-bis(diphenylphosphanyl)-1'-(diisopropylphosphanyl)-3'-(triphenyl)methyl-4-tert-butyl ferrocene, 11. In particular, the existence of a range of significantly different nonbonded ("through-space", TS) spin-spin coupling constants between heteroannular P atoms, for the triphosphanes of this class, allowed their preferred conformation in solution to be appraised. The study evidences an unanticipated flexibility of the ferrocene platform, despite the presence of very congested tert-butyl and trityl groups. Herein, we show that, contrary to our first belief, the preferred conformation for the backbone of ferrocenyl polyphosphanes can not only depend on the hindrance of the groups decorating the cyclopentadienyl rings but is also a function of the substituents of the phosphanyl groups. The interest of these robust phosphanes as ligands was illustrated in palladium catalysis for the arylation of n-butyl furan with chloroarenes, using direct C-H activation of the heteroaromatic in the presence of low metal/ligand loadings (0.5-1.0 mol %). Thus, 4-chlorobenzonitrile, 4-chloronitrobenzene, 4-chloropropiophenone, and 4-(trifluoromethyl)chlorobenzene were efficiently coupled to n-butyl furan, using Pd(OAc)(2) associated to the new diphosphane ligands 1,1'-bis(diisopropylphosphanyl)-3,3'-di(triphenyl)methyl ferrocene (15) or 1,1'-bis(dicyclohexylphosphanyl)-3,3'-di(triphenyl)methylferrocene (16), which respectively hold the electron-rich -Pi-Pr(2) and -PCy(2) groups.

Infrared Fingerprints of nN → σ*NH Hyperconjugation in Hydrazides.

PubMed

Andrade, Laize A F; Silla, Josué M; Cormanich, Rodrigo A; Freitas, Matheus P

2017-12-01

An earlier study demonstrated that hyperconjugation operates in hydrazides by analyzing the N-H stretching mode in gas phase infrared (IR) spectroscopy, and then observing two very distinct bands corresponding to isolated isomers experiencing or not the n N → σ* N-H electron delocalization. The present work reports a chemical method to obtain insight on the hyperconjugation in hydrazide derivatives from solution IR spectroscopy. The analogous amides did not show a ν N-H red-shifted band, as the electron donor orbital in the above hyperconjugative interaction does not exist. In addition, the effect of electron withdrawing groups bonded to a nitrogen atom, namely the trifluoroacetyl and the methanesulfonyl groups, was analyzed on the conformational isomerism and on the ability to induce a stronger hyperconjugation in the resulting compounds.

Synthesis and characterization of highly photoresponsive fullerenyl dyads with a close chromophore antenna–C60 contact and effective photodynamic potential†

PubMed Central

Padmawar, Prashant A.; Rogers-Haley, Joy E.; So, Grace; Canteenwala, Taizoon; Thota, Sammaiah; Tan, Loon-Seng; Pritzker, Kenneth; Huang, Ying-Ying; Sharma, Sulbha K.; Kurup, Divya Balachandran; Hamblin, Michael R.; Wilson, Brian; Urbas, Augustine

2010-01-01

We report the synthesis of a new class of photoresponsive C60–DCE–diphenylaminofluorene nanostructures and their intramolecular photoinduced energy and electron transfer phenomena. Structural modification was made by chemical conversion of the keto group in C60(>DPAF-Cn) to a stronger electron-withdrawing 1,1-dicyanoethylenyl (DCE) unit leading to C60(>CPAF-Cn) with an increased electronic polarization of the molecule. The modification also led to a large bathochromic shift of the major band in visible spectrum giving measureable absorption up to 600 nm and extended the photoresponsive capability of C60–DCE–DPAF nanostructures to longer red wavelengths than C60(>DPAF-Cn). Accordingly, C60(>CPAF-Cn) may allow 2γ-PDT using a light wavelength of 1000–1200 nm for enhanced tissue penetration depth. Production efficiency of singlet oxygen by closely related C60(>DPAF-C2M) was found to be comparable with that of tetraphenylporphyrin photosensitizer. Remarkably, the 1O2 quantum yield of C60(>CPAF-C2M) was found to be nearly 6-fold higher than that of C60(>DPAF-C2M), demonstrating the large light-harvesting enhancement of the CPAF-C2M moiety and leading to more efficient triplet state generation of the C60> cage moiety. This led to highly effective killing of HeLa cells by C60(>CPAF-C2M) via photodynamic therapy (200 J cm−2 white light). We interpret the phenomena in terms of the contributions by the extended π-conjugation and stronger electron-withdrawing capability associated with the 1,1-dicyanoethylenyl group compared to that of the keto group. PMID:20890406

Bio-inspired cofacial Fe porphyrin dimers for efficient electrocatalytic CO2 to CO conversion: Overpotential tuning by substituents at the porphyrin rings

PubMed Central

Zahran, Zaki N.; Mohamed, Eman A.; Naruta, Yoshinori

2016-01-01

Efficient reduction of CO2 into useful carbon resources particularly CO is an essential reaction for developing alternate sources of fuels and for reducing the greenhouse effect of CO2. The binuclear Ni, Fe−containing carbon monoxide dehydrogenase (CODHs) efficiently catalyzes the reduction of CO2 to CO. The location of Ni and Fe at proper positions allows their cooperation for CO2 to CO conversion through a push−pull mechanism. Bio−inspired from CODHs, we used several cofacial porphyrin dimers with different substituents as suitable ligands for holding two Fe ions with suitable Fe−Fe separation distance to efficiently and selectively promote CO2 to CO conversion with high turnover frequencies, TOFs. The substituents on the porphyrin rings greatly affect the catalysis process. By introducing electron-withdrawing/-donating groups, e.g. electron-withdrawing perfluorophenyl, at all meso positions of the porphyrin rings, the catalysis overpotential, η was minimized by ≈0.3 V compared to that obtained by introducing electron-donating mesityl groups. The Fe porphyrin dimers among reported catalysts are the most efficient ones for CO2 to CO conversion. Control experiments indicate that the high performance of the current CO2 to CO conversion catalysts is due to the presence of binuclear Fe centers at suitable Fe−Fe separation distance. PMID:27087483

Bio-inspired cofacial Fe porphyrin dimers for efficient electrocatalytic CO2 to CO conversion: Overpotential tuning by substituents at the porphyrin rings.

PubMed

Zahran, Zaki N; Mohamed, Eman A; Naruta, Yoshinori

2016-04-18

Efficient reduction of CO2 into useful carbon resources particularly CO is an essential reaction for developing alternate sources of fuels and for reducing the greenhouse effect of CO2. The binuclear Ni, Fe-containing carbon monoxide dehydrogenase (CODHs) efficiently catalyzes the reduction of CO2 to CO. The location of Ni and Fe at proper positions allows their cooperation for CO2 to CO conversion through a push-pull mechanism. Bio-inspired from CODHs, we used several cofacial porphyrin dimers with different substituents as suitable ligands for holding two Fe ions with suitable Fe-Fe separation distance to efficiently and selectively promote CO2 to CO conversion with high turnover frequencies, TOFs. The substituents on the porphyrin rings greatly affect the catalysis process. By introducing electron-withdrawing/-donating groups, e.g. electron-withdrawing perfluorophenyl, at all meso positions of the porphyrin rings, the catalysis overpotential, η was minimized by ≈0.3 V compared to that obtained by introducing electron-donating mesityl groups. The Fe porphyrin dimers among reported catalysts are the most efficient ones for CO2 to CO conversion. Control experiments indicate that the high performance of the current CO2 to CO conversion catalysts is due to the presence of binuclear Fe centers at suitable Fe-Fe separation distance.

Bio-inspired cofacial Fe porphyrin dimers for efficient electrocatalytic CO2 to CO conversion: Overpotential tuning by substituents at the porphyrin rings

NASA Astrophysics Data System (ADS)

Zahran, Zaki N.; Mohamed, Eman A.; Naruta, Yoshinori

2016-04-01

Efficient reduction of CO2 into useful carbon resources particularly CO is an essential reaction for developing alternate sources of fuels and for reducing the greenhouse effect of CO2. The binuclear Ni, Fe-containing carbon monoxide dehydrogenase (CODHs) efficiently catalyzes the reduction of CO2 to CO. The location of Ni and Fe at proper positions allows their cooperation for CO2 to CO conversion through a push-pull mechanism. Bio-inspired from CODHs, we used several cofacial porphyrin dimers with different substituents as suitable ligands for holding two Fe ions with suitable Fe-Fe separation distance to efficiently and selectively promote CO2 to CO conversion with high turnover frequencies, TOFs. The substituents on the porphyrin rings greatly affect the catalysis process. By introducing electron-withdrawing/-donating groups, e.g. electron-withdrawing perfluorophenyl, at all meso positions of the porphyrin rings, the catalysis overpotential, η was minimized by ≈0.3 V compared to that obtained by introducing electron-donating mesityl groups. The Fe porphyrin dimers among reported catalysts are the most efficient ones for CO2 to CO conversion. Control experiments indicate that the high performance of the current CO2 to CO conversion catalysts is due to the presence of binuclear Fe centers at suitable Fe-Fe separation distance.

Label-Free Proteomic Analysis of Protein Changes in the Striatum during Chronic Ethanol Use and Early Withdrawal

PubMed Central

Ayers-Ringler, Jennifer R.; Oliveros, Alfredo; Qiu, Yanyan; Lindberg, Daniel M.; Hinton, David J.; Moore, Raymond M.; Dasari, Surendra; Choi, Doo-Sup

2016-01-01

The molecular mechanisms underlying the neuronal signaling changes in alcohol addiction and withdrawal are complex and multifaceted. The cortico-striatal circuit is highly implicated in these processes, and the striatum plays a significant role not only in the early stages of addiction, but in the developed-addictive state as well, including withdrawal symptoms. Transcriptional analysis is a useful method for determining changes in gene expression, however, the results do not always accurately correlate with protein levels. In this study, we employ label-free proteomic analysis to determine changes in protein expression within the striatum during chronic ethanol use and early withdrawal. The striatum, composed primarily of medium spiny GABAergic neurons, glutamatergic and dopaminergic nerve terminals and astrocytes, is relatively homogeneous for proteomic analysis. We were able to analyze more than 5000 proteins from both the dorsal (caudate and putamen) and ventral (nucleus accumbens) striatum and identified significant changes following chronic intermittent ethanol exposure and acute (8 h) withdrawal compared to ethanol naïve and ethanol exposure groups respectively. Our results showed significant changes in proteins involved in glutamate and opioid peptide signaling, and also uncovered novel pathways including mitochondrial function and lipid/cholesterol metabolism, as revealed by changes in electron transport chain proteins and RXR activation pathways. These results will be useful in the development of novel treatments for alcohol withdrawal and thereby aid in recovery from alcohol use disorder. PMID:27014007

Trajectories of Social Withdrawal from Grades 1 to 6: Prediction from Early Parenting, Attachment, and Temperament

PubMed Central

Booth-LaForce, Cathryn; Oxford, Monica L.

2015-01-01

From 1092 children in the NICHD Study of Early Child Care and Youth Development, we identified three trajectory patterns of social withdrawal from teacher reports in Grades 1-6: A Normative consistently low group (86%); a Decreasing group (5%) with initially high withdrawal that decreased; and an Increasing group (9%) with initially low withdrawal that increased. Prediction models supported the role of early dysregulated temperament, insensitive parenting, and attachment. Preschool shy temperament was a specific pathway to decreasing withdrawal, and poor inhibitory control, to increasing withdrawal. Children on the increasing pathway were more lonely, solitary, and excluded by peers. Results suggest differentiated pathways to varying trajectories of social withdrawal and highlight the importance of identification of longitudinal patterns in relation to risk. PMID:18793064

Regioselective copper-catalyzed N(1)-(hetero)arylation of protected histidine.

PubMed

Sharma, Krishna K; Mandloi, Meenakshi; Jain, Rahul

2016-09-26

We report regioselective N(1)-arylation of protected histidine using copper(i) iodide as a catalyst, trans-N,N'-dimethylcyclohexane-1,2-diamine as a ligand and readily available aryl iodides as coupling partners under microwave irradiation at 130 °C for 40 min. The reaction provides rapid access to electron-donating, electron-withdrawing and bulky group substituted N-arylated histidines in high yields, including previously inaccessible N-heteroaryl histidines. These N(1)-(hetero)aryl histidines are promising building blocks in peptide-based drug design and discovery.

New Stable Cu(I) Catalyst Supported on Weakly Acidic Polyacrylate Resin for Green C-N Coupling: Synthesis of N-(Pyridin-4-yl)benzene Amines and N,N-Bis(pyridine-4-yl)benzene Amines.

PubMed

Kore, Nitin; Pazdera, Pavel

2016-12-22

A method for preparation of a new stable Cu(I) catalyst supported on weakly acidic polyacrylate resin without additional stabilizing ligands is described. A simple and efficient methodology for Ullmann Cu(I) catalyzed C-N cross coupling reactions using this original catalyst is reported. Coupling reactions of 4-chloropyridinium chloride with anilines containing electron donating (EDG) or electron withdrawing (EWG) groups, naphthalen-2-amine and piperazine, respectively, are successfully demonstrated.

Aryl sulfonate based anticancer alkylating agents.

PubMed

Sheikh, Hamdullah Khadim; Arshad, Tanzila; Kanwal, Ghazala

2018-05-01

This research work revolves around synthesis of antineoplastic alkylating sulfonate esters with dual alkylating sites for crosslinking of the DNA strands. These molecules were evaluated as potential antineoplastic cross linking alkylating agents by reaction with the nucleoside of Guanine DNA nucleobase at both ends of the synthesized molecule. Synthesis of the alkylating molecules and the crosslinking with the guanosine nucleoside was monitored by MALDITOF mass spectroscopy. The synthesized molecule's crosslinking or adduct forming rate with the nucleoside was compared with that of 1,4 butane disulfonate (busulfan), in form of time taken for the appearance of [M+H] + . It was found that aryl sulfonate leaving group was causing higher rate of nucleophilic attack by the Lewis basic site of the nucleobase. Furthermore, the rate was also found to be a function of electron withdrawing or donating nature of the substituent on the aryl ring. Compound with strong electron withdrawing substituent on the para position of the ring reacted fastest. Hence, new alkylating agents were synthesized with optimized or desired reactivity.

Core Perylene Diimide Designs via Direct Bay- and ortho-(Poly)trifluoromethylation: Synthesis, Isolation, X-Ray Structures, Optical and Electronic Properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clikeman, Tyler T.; Bukovsky, Eric V.; Wang, Xue-Bin

2015-09-22

We developed an efficient solvent- and catalyst-free direct polytrifluoromethylation of solid perylene-3,4,9,10-tetracarboxylic dianhydride that produced a new family of (poly)perfluoroalkyl bay- and ortho-substituted PDIs with two different imide substituents. Direct hydrogen substitution with CN group led to the synthesis of a cyanated perfluoroalkyl PDI derivative for the first time. Absorption, steady-state and time-resolved emission, X-ray diffraction, electrochemical, and gas-phase electron affinity data allowed for systematic studies of substitution effects at bay, ortho, and imide positions in the new PDIs. Solid-state packing showed remarkable variations in the intermolecular interactions that are important for charge transport and photophysical properties. Moreover, analysis ofmore » the electrochemical data for 143 electron poor PDIs, including newly reported compounds, revealed some general trends and peculiar effects from substituting electron-withdrawing groups at all three positions.« less

Core Perylene Diimide Designs via Direct Bay and Ortho (Poly)trifluoromethylation: Synthesis, Isolation, X-ray Structures, Optical and Electronic Properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clikeman, Tyler T.; Bukovsky, Eric V.; Wang, Xue B.

2015-09-22

We developed an efficient solvent- and catalyst-free direct polytrifluoromethylation of solid perylene-3,4,9,10-tetracarboxylic dianhydride that produced a new family of (poly)perfluoroalkyl bay and ortho substituted PDIs with two different imide substituents. Direct hydrogen substitution with CN group led to the synthesis of a cyanated perfluoroalkyl PDI derivative for the first time. Absorption, steady-state and time-resolved emission, X-ray diffraction, electrochemical, and gas-phase electron affinity data allowed for systematic studies of substitution effects at bay, ortho, and imide positions in the new PDIs. Solid-state packing showed remarkable variations in the intermolecular interactions that are important for charge transport and photophysical properties. Analysis ofmore » the electrochemical data for 143 electron poor PDIs, including newly reported compounds, revealed some general trends and peculiar effects of electron withdrawing group substitution at all three positions.« less

The prevalence and correlates of severe social withdrawal (hikikomori) in Hong Kong: A cross-sectional telephone-based survey study.

PubMed

Wong, Paul W C; Li, Tim M H; Chan, Melissa; Law, Y W; Chau, Michael; Cheng, Cecilia; Fu, K W; Bacon-Shone, John; Yip, Paul S F

2015-06-01

Severe social withdrawal behaviors among young people have been a subject of public and clinical concerns. This study aimed to explore the prevalence of social withdrawal behaviors among young people aged 12-29 years in Hong Kong. A cross-sectional telephone-based survey was conducted with 1,010 young individuals. Social withdrawal behaviors were measured with the proposed research diagnostic criteria for hikikomori and were categorized according to the (a) international proposed duration criterion (more than 6 months), (b) local proposed criterion (less than 6 months) and (c) with withdrawal behaviors but self-perceived as non-problematic. The correlates of social withdrawal among the three groups were examined using multinomial and ordinal logistic regression analyses. The prevalence rates of more than 6 months, less than 6 months and self-perceived non-problematic social withdrawal were 1.9%, 2.5% and 2.6%, respectively. In terms of the correlates, the internationally and locally defined socially withdrawn youths are similar, while the self-perceived non-problematic group is comparable to the comparison group. The study finds that the prevalence of severe social withdrawal in Hong Kong is comparable to that in Japan. Both groups with withdrawal behaviors for more or less than 6 months share similar characteristics and are related to other contemporary youth issues, for example, compensated dating and self-injury behavior. The self-perceived non-problematic group appears to be a distinct group and the withdrawal behaviors of its members may be discretionary. © The Author(s) 2014.

Ynamides in Ring Forming Transformations

PubMed Central

WANG, XIAO-NA; YEOM, HYUN-SUK; FANG, LI-CHAO; HE, SHUZHONG; MA, ZHI-XIONG; KEDROWSKI, BRANT L.; HSUNG, RICHARD P.

2013-01-01

Conspectus The ynamide functional group activates carbon-carbon triple bonds through an attached nitrogen atom that bears an electron-withdrawing group. As a result, the alkyne has both electrophilic and nucleophilic properties. Through the selection of the electron-withdrawing group attached to nitrogen chemists can modulate the electronic properties and reactivity of ynamides, making these groups versatile synthetic building blocks. The reactions of ynamides also lead directly to nitrogen-containing products, which provides access to important structural motifs found in natural products and molecules of medicinal interest. Therefore, researchers have invested increasing time and research in the chemistry of ynamides in recent years. This Account surveys and assesses new organic transformations involving ynamides developed in our laboratory and in others around the world. We showcase the synthetic power of ynamides for rapid assembly of complex molecular structures. Among the recent reports of ynamide transformations, ring-forming reactions provide a powerful tool for generating molecular complexity quickly. In addition to their synthetic utility, such reactions are mechanistically interesting. Therefore, we focus primarily on the cyclization chemistry of ynamides. This Account highlights ynamide reactions that are useful in the rapid synthesis of cyclic and polycyclic structural manifolds. We discuss the mechanisms active in the ring formations and describe representative examples that demonstrate the scope of these reactions and provide mechanistic insights. In this discussion we feature examples of ynamide reactions involving radical cyclizations, ring-closing metathesis, transition metal and non-transition metal mediated cyclizations, cycloaddition reactions, and rearrangements. The transformations presented rapidly introduce structural complexity and include nitrogen within, or in close proximity to, a newly formed ring (or rings). Thus, ynamides have emerged as powerful synthons for nitrogen-containing heterocycles and nitrogen-substituted rings, and we hope this Account will promote continued interest in the chemistry of ynamides. PMID:24164363

Can Electron-Rich Oxygen (O2-) Withdraw Electrons from Metal Centers? A DFT Study on Oxoanion-Caged Polyoxometalates.

PubMed

Takazaki, Aki; Eda, Kazuo; Osakai, Toshiyuki; Nakajima, Takahito

2017-10-12

The answer to the question "Can electron-rich oxygen (O 2- ) withdraw electrons from metal centers?" is seemingly simple, but how the electron population on the M atom behaves when the O-M distance changes is a matter of controversy. A case study has been conducted for Keggin-type polyoxometalate (POM) complexes, and the first-principles electronic structure calculations were carried out not only for real POM species but also for "hypothetical" ones whose heteroatom was replaced with a point charge. From the results of natural population analysis, it was proven that even an electron-rich O 2- , owing to its larger electronegativity as a neutral atom, withdraws electrons when electron redistribution occurs by the change of the bond length. In the case where O 2- coexists with a cation having a large positive charge (e.g., P 5+ (O 2- ) 4 = [PO 4 ] 3- ), the gross electron population (GEP) on the M atom seemingly increases as the O atom comes closer, but this increment in GEP is not due to the role of the O atom but due to a Coulombic effect of the positive charge located on the cation. Furthermore, it was suggested that not GEP but net electron population (NEP) should be responsible for the redox properties.

[Alcohol withdrawal syndrome dynamics during treatment with nooclerin (deanoli aceglumas)].

PubMed

Agibalova, T V; Buzik, O Zh; Rychkova, O V; Smyshlyaev, A V; Rumbesht, V V

2018-01-01

To study the efficacy of nooclerin (deanoli aceglumas) in alcohol withdrawal syndrome assessed by clinical and biochemical characteristics. A multicenter, open, randomized, comparative study of nooclerin in the complex treatment of alcohol withdrawal syndrome included 90 patients. The patients were randomized into nooclerin group (n=55) and control group (n=35). Nooclerin reduced alcohol withdrawal symptoms more significantly throughout the whole study period. There were significant between-group differences on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) and the Multidimensional Fatigue Inventory (МFI-20). However, patients exhibited no excessive activity. No adverse side-effects were observed.

Computationally designed and experimentally confirmed diastereoselective rhodium-catalyzed Pauson-Khand reaction at room temperature.

PubMed

Baik, Mu-Hyun; Mazumder, Shivnath; Ricci, Paolo; Sawyer, James R; Song, Ye-Geun; Wang, Huijun; Evans, P Andrew

2011-05-25

The computational analysis of the rhodium-catalyzed Pauson-Khand reaction indicates that the key transition state is highly charge-polarized, wherein different diastereoisomers have distinctively different charge polarization patterns. Experimental studies demonstrate that chloro-enynes provide the optimal σ-electron-withdrawing group to promote polarization and thereby reduce the activation barrier to provide a highly diastereoselective reaction at room temperature.

Mild and efficient molybdenum-mediated Pauson-Khand-type reaction.

PubMed

Adrio, Javier; Rivero, Marta Rodríguez; Carretero, Juan Carlos

2005-02-03

[reaction: see text] The molybdenum-mediated Pauson-Khand reaction promoted by Mo(CO)3(DMF)3 takes place under very mild conditions in the absence of any promoter. High yields in Pauson-Khand adducts are obtained in the cyclization of a wide variety of functionalized 1,6- and 1,7-enynes. Enynes bearing electron withdrawing groups at the alkene terminus are particularly good substrates.

Computational insight into the reaction intermediates in the glycosylation reaction assisted by donor heteroatoms.

PubMed

Bravo, Fernando; Viso, Antonio; Alcázar, Eva; Molas, Pineda; Bo, Carles; Castillón, Sergio

2003-02-07

We studied the geometric and electronic structure of several cations (9 and 18-23) that are usually proposed as intermediates for glycosylation reactions using DFT methods. For ions 9 and 18-23 the geometries obtained corresponded to an open ion (6b type) irrespective of the exocyclic heteroatom (S, Se, I) and the size of the cycle (furanoses as well as pyranoses). We studied how substituents bonded to the exocyclic heteroatom (R in SR and SeR) affect the structure of ions and found that the geometry approached that of episulfonium and episelenonium ions (6a type) when the substituents were electron donors. The tert-butyl group and the 2,4,6-trimethyl- and 2,4,6-trimethoxyphenyl and trimethylsilyl groups produced the strongest of these effects. The presence of an electron-withdrawing group (CO-CF(3)) bonded to the hydroxymethyl group produced a similar but weaker effect. We analyzed this behavior in terms of molecular orbital interactions.

Kinetic and Mechanistic Examination of Acid–Base Bifunctional Aminosilica Catalysts in Aldol and Nitroaldol Condensations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collier, Virginia E.; Ellebracht, Nathan C.; Lindy, George I.

The kinetic and mechanistic understanding of cooperatively catalyzed aldol and nitroaldol condensations is probed using a series of mesoporous silicas functionalized with aminosilanes to provide bifunctional acid–base character. Mechanistically, a Hammett analysis is performed to determine the effects of electron-donating and electron-withdrawing groups of para-substituted benzaldehyde derivatives on the catalytic activity of each condensation reaction. This information is also used to discuss the validity of previously proposed catalytic mechanisms and to propose a revised mechanism with plausible reaction intermediates. For both reactions, electron-withdrawing groups increase the observed rates of reaction, though resonance effects play an important, yet subtle, role inmore » the nitroaldol condensation, in which a p-methoxy electron-donating group is also able to stabilize the proposed carbocation intermediate. Additionally, activation energies and pre-exponential factors are calculated via the Arrhenius analysis of two catalysts with similar amine loadings: one catalyst had silanols available for cooperative interactions (acid–base catalysis), while the other was treated with a silanol-capping reagent to prevent such cooperativity (base-only catalysis). The values obtained for activation energies and pre-exponential factors in each reaction are discussed in the context of the proposed mechanisms and the importance of cooperative interactions in each reaction. The catalytic activity decreases for all reactions when the silanols are capped with trimethylsilyl groups, and higher temperatures are required to make accurate rate measurements, emphasizing the vital role the weakly acidic silanols play in the catalytic cycles. The results indicate that loss of acid sites is more detrimental to the catalytic activity of the aldol condensation than the nitroaldol condensation, as evidenced by the significant decrease in the pre-exponential factor for the aldol condensation when silanols are unavailable for cooperative interactions. Cooperative catalysis is evidenced by significant changes in the pre-exponential factor, rather than the activation energy for the aldol condensation.« less

Kinetic and Mechanistic Examination of Acid–Base Bifunctional Aminosilica Catalysts in Aldol and Nitroaldol Condensations

DOE PAGES

Collier, Virginia E.; Ellebracht, Nathan C.; Lindy, George I.; ...

2015-12-09

The kinetic and mechanistic understanding of cooperatively catalyzed aldol and nitroaldol condensations is probed using a series of mesoporous silicas functionalized with aminosilanes to provide bifunctional acid–base character. Mechanistically, a Hammett analysis is performed to determine the effects of electron-donating and electron-withdrawing groups of para-substituted benzaldehyde derivatives on the catalytic activity of each condensation reaction. This information is also used to discuss the validity of previously proposed catalytic mechanisms and to propose a revised mechanism with plausible reaction intermediates. For both reactions, electron-withdrawing groups increase the observed rates of reaction, though resonance effects play an important, yet subtle, role inmore » the nitroaldol condensation, in which a p-methoxy electron-donating group is also able to stabilize the proposed carbocation intermediate. Additionally, activation energies and pre-exponential factors are calculated via the Arrhenius analysis of two catalysts with similar amine loadings: one catalyst had silanols available for cooperative interactions (acid–base catalysis), while the other was treated with a silanol-capping reagent to prevent such cooperativity (base-only catalysis). The values obtained for activation energies and pre-exponential factors in each reaction are discussed in the context of the proposed mechanisms and the importance of cooperative interactions in each reaction. The catalytic activity decreases for all reactions when the silanols are capped with trimethylsilyl groups, and higher temperatures are required to make accurate rate measurements, emphasizing the vital role the weakly acidic silanols play in the catalytic cycles. The results indicate that loss of acid sites is more detrimental to the catalytic activity of the aldol condensation than the nitroaldol condensation, as evidenced by the significant decrease in the pre-exponential factor for the aldol condensation when silanols are unavailable for cooperative interactions. Cooperative catalysis is evidenced by significant changes in the pre-exponential factor, rather than the activation energy for the aldol condensation.« less

Tests and refinements of a general structure-activity model for avian repellents.

PubMed

Clark, L; Shah, P

1994-02-01

We tested the robustness of a structure-activity model for avian trigeminal chemoirritants. Fourteen benzoates and acetophenones were tested using European starlingsSturnus vulgaris as a bioassay. In general, the previously proposed model was a reasonable predictor of repellency (i.e., irritant potency). We found that the presence of a phenyl ring was critical to repellency. Basicity of the molecule is the next most critical feature influencing repellency. The presence of an acidic function within the electron-withdrawing functionality seriously detracts from repellency. The presence or absence of an electron-withdrawing or -donating group may potentiate repellent effects, but its presence is not critical, so long as the phenyl ring is electron rich. Our data suggest that there is ano-aminoacetophenone/methyl anthranilate trigeminal chemoreceptor in birds analogous to the mammalian capsaicin receptor. Both receptors contain a benzene site. However, birds seem to lack the associated thiol/hydrogen-bonding site present in mammals which is needed to activate the benzene site. Rather, birds may possess an associated exposed charged site that in turn may interact with the stimulus to activate the benzene site. These differences may explain the differential sensitivity of birds and mammals to aromatic irritants.

The Effect of Co-occurring Substance Use on Gamma-hydroxybutyric Acid Withdrawal Syndrome.

PubMed

Kamal, Rama M; Dijkstra, Boukje A G; Loonen, Anton J; De Jong, Cornelis A J

2016-01-01

Gamma-hydroxybutyric acid (GHB) withdrawal is a complex syndrome which can be potentially life-threatening. Additionally, GHB-dependent patients frequently report co-occurring substance use of other psychoactive drugs. We assessed the add-on effect of co-use on GHB withdrawal symptoms. We conducted an open-label, pretest-posttest design study with 95 patients selected from 229 inpatients admitted for detoxification, who were divided into GHB only (GO, n = 40), GHB plus sedatives (GSE, n = 38), and GHB plus stimulants (GST, n = 17) groups. GHB withdrawal was evaluated by means of the Subjective Withdrawal Scale. Co-use add-on effects on the severity of withdrawal symptoms were evaluated 2.5 hours after the last illicit GHB self-administration (T1) when withdrawal was expected and 2.5 hours later, after administration of a very low dose of pharmaceutical GHB (T2). The GO group reported high scores of psychomotor retardation symptoms at both T1 and T2, and also high cravings, agitation, and restlessness at T1, and anxiety at T2. The GSE group reported the highest score in psycho-autonomic distress symptoms at both T1 and T2, whereas the GST group reported the highest score in psycho-motor stress factor at T2. There was no significant difference in withdrawal intensity in all symptom clusters between T1 and T2 for both GSE and GO groups. However, after 5 hours, the GST group reported significant decreases in intensity for all symptoms except for psycho-motor stress. At T1, GST and GSE groups reported more muscle twitches than the GO group as a significant add-on effect to the GHB withdrawal. At T2, the GST group experienced more agitation (P = 0.009), restlessness (P = 0.001), and rapid pulse (P = 0.034) than the GO group. Co-use, especially of stimulants, caused an add-on effect on the GHB withdrawal symptoms within the first 5 hours.

Theoretical study of X⁻ · 1 · YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH₂ and AsH₂): noncovalently electron-withdrawing effects on anion-arene interactions.

PubMed

Chen, Yishan; Yao, Lifeng

2014-01-01

The ternary complexes X(-) · 1 · YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH2 and AsH2) have been investigated by MP2 calculations to understand the noncovalently electron-withdrawing effects on anion-arene interactions. The results indicate that in binary complexes (1 · X(-)), both weak σ-type and anion-π complexes can be formed for Cl(-) and Br(-), but only anion-π complex can be formed for I(-). Moreover, the hydrogen-bonding complex is the global minimum for all three halides in binary complexes. However, in ternary complexes, anion-π complex become unstable and only σ complex can retain in many cases for Cl(-) and Br(-). Anion-π complex keeps stable only when YF = HF. In contrast with binary complexes, σ complex become the global minimum for Cl(-) and Br(-) in ternary complexes. These changes in binding mode and strength are consistent with the results of covalently electron-withdrawing effects. However, in contrast with the covalently electron-withdrawing substituents, Cl(-) and Br(-) can attack the aromatic carbon atom to form a strong σ complex when the noncovalently electron-withdrawing effect is induced by halogen bonding. The binding behavior for I(-) is different from that for Cl(-) and Br(-) in two aspects. First, the anion-π complex for I(-) can also keep stable when the noncovalent interaction is halogen bonding. Second, the anion-π complex for I(-) is the global minimum when it can retain as a stable structure.

Effect of Pulsed Radiofrequency on Rat Sciatic Nerve Chronic Constriction Injury: A Preliminary Study

PubMed Central

Li, Duo-Yi; Meng, Lan; Ji, Nan; Luo, Fang

2015-01-01

Background: Pulsed radiofrequency (PRF) application to the dorsal root ganglia can reduce neuropathic pain (NP) in animal models, but the effect of PRF on damaged peripheral nerves has not been examined. We investigated the effect of PRF to the rat sciatic nerve (SN) on pain-related behavior and SN ultrastructure following chronic constriction injury (CCI). Methods: The analgesic effect was measured by hindpaw mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Twenty rats with NP induced by ligating the common SN were then randomly divided into a PRF treatment group and a sham group. The contralateral SN served as a control. The MWT and TWL were determined again 2, 4, 6, 8, 10, 12, and 14 days after the PRF or sham treatment. On day 14, ipsilateral and contralateral common SNs were excised and examined by electron microscopy. Results: Ipsilateral MWT was significantly reduced and TWL significantly shorter compared to the contralateral side 14 days after CCI (both P = 0.000). In the PRF group, MWT was significantly higher and TWL significantly longer 14 days after the PRF treatment compared to before PRF treatment (both P = 0.000), while no such difference was observed in the sham group (P > 0.05). Electron microscopy revealed extensive demyelination and collagen fiber formation in the ipsilateral SN of sham-treated rats but sparse demyelination and some nerve fiber regrowth in the PRF treatment group. Conclusions: Hyperalgesia is relieved, and ultrastructural damage ameliorated after direct PRF treatment to the SN in the CCI rat model of NP. PMID:25673460

The Substituent Effects on π-type Pnicogen Bond Interaction

NASA Astrophysics Data System (ADS)

Zhu, Jian-Qing; Cao, Sheng-Wei; Wang, Wei; Xu, Xiao-Lu; Xu, Hui-Ying

2017-05-01

Intermolecular interactions between PH2Cl and Ar-R (R=H, OH, NH2, CH3, Br, Cl, F, CN, NO2) were calculated by using MP2/aug-cc-pVDZ quantum chemical method. It has been shown from our calculations that the aromatic rings with electron-withdrawing groups represent much weaker binding affinities than those with electron-donating groups. The charge-transfer interaction between PH2Cl and Ar-R plays an important role in the formation of pnicogen bond complexes, as revealed by NBO analysis. The π-type halogen bond was also calculated and comparison of these two π-type interactions was made. It has been revealed that the π-type pnicogen bond systems are more stable than the halogen bond ones.

Intramolecular interactions in polymethylenic chains with polar end groups: The spectroscopic signature

NASA Astrophysics Data System (ADS)

Milani, Alberto; Castiglioni, Chiara; Brambilla, Luigi; Zerbi, Giuseppe

2012-02-01

We present a computational study based on DFT simulations of the infrared spectra of several short alkyl chains carrying polar end groups. The work aims to provide guidelines for the detection of marker bands signalling the occurrence of specific intramolecular interactions between the polar head and CH2 groups at different distances. In particular, the CH stretching region is investigated and new features assigned to normal modes localized on the CH2 groups nearest to the electron-withdrawing atom are identified. The study has been extended also to the rationalization of the experimental IR features shown by a 1-Chloroeicosane (C20H41Cl) sample.

2,3-Dihydroxybenzoic acid amides of tetraazaalkanes and tetaaza cycloalkanes

DOEpatents

Weitl, Frederick L. [Martinez, CA; Raymond, Kenneth N. [Berkeley, CA

1980-01-01

A compound of the formula: ##STR1## wherein X is hydrogen or a conventional electron-withdrawing group, particularly --SO.sub.3 H or a salt thereof; n is 2, 3, or 4; m is 2, 3, or 4; and p is 2 or 3. The present compounds are useful as specific sequestering agents for actinide (IV) ions. Also described is a method for the 2,3-dihydroxybenzamidation of azaalkanes.

Solar photochemical oxidations of benzylic and allylic alcohols using catalytic organo-oxidation with DDQ: application to lignin models.

PubMed

Walsh, Katie; Sneddon, Helen F; Moody, Christopher J

2014-10-03

Visible light has a dramatic effect on the oxidation of benzylic and allylic alcohols, including those deactivated by electron-withdrawing groups, and β-O-4 lignin models, using catalytic amounts of the organo-oxidant 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. Sodium nitrite or tert-butyl nitrite is used as cocatalyst, and oxygen is employed as the terminal oxidant.

A novel base-induced isomerization gives access to unprecedented (E)-exo-glycals.

PubMed

Eppe, Guillaume; Dumitrescu, Lidia; Pierrot, Olivier; Li, Tianlei; Pan, Weidong; Vincent, Stéphane P

2013-08-26

Bump the base: This study reports the discovery of the base-induced Z-to-E isomerization of exo-glycals bearing an electron-withdrawing group (EWG). The scope of this novel transformation regarding the carbohydrate unit is also discussed. After elucidating the mechanism, preparation of novel (E)-exo- glycals was performed (TBS = tert-butyldimethylsilyl). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel Halogenated Pyrazine-Based Chalcones as Potential Antimicrobial Drugs.

PubMed

Kucerova-Chlupacova, Marta; Vyskovska-Tyllova, Veronika; Richterova-Finkova, Lenka; Kunes, Jiri; Buchta, Vladimir; Vejsova, Marcela; Paterova, Pavla; Semelkova, Lucia; Jandourek, Ondrej; Opletalova, Veronika

2016-10-27

Chalcones, i.e., compounds with the chemical pattern of 1,3-diphenylprop-2-en-1-ones, exert a wide range of bio-activities, e.g., antioxidant, anti-inflammatory, anticancer, anti-infective etc. Our research group has been focused on pyrazine analogues of chalcones; several series have been synthesized and tested in vitro on antifungal and antimycobacterial activity. The highest potency was exhibited by derivatives with electron withdrawing groups (EWG) in positions 2 and 4 of the ring B. As halogens also have electron withdrawing properties, novel halogenated derivatives were prepared by Claisen-Schmidt condensation. All compounds were submitted for evaluation of their antifungal and antibacterial activity, including their antimycobacterial effect. In the antifungal assay against eight strains of selected fungi, growth inhibition of Candida glabrata and Trichophyton interdigitale (formerly T. mentagrophytes ) was shown by non-alkylated derivatives with 2-bromo or 2-chloro substitution. In the panel of selected bacteria, 2-chloro derivatives showed the highest inhibitory effect on Staphylococcus sp. In addition, all products were also screened for their antimycobacterial activity against Mycobacterium tuberculosis H37RV My 331/88, M. kansasii My 235/80, M. avium 152/80 and M. smegmatis CCM 4622. Some of the examined compounds, inhibited growth of M. kansasii and M. smegmatis with minimum inhibitory concentrations (MICs) comparable with those of isoniazid.

Singlet-triplet energy differences in divalent five membered cyclic conjugated Arduengo-type carbenes XC2HN2M (M = C, Si, Ge, Sn, and Pb; X = F, Cl, Br, and I)

NASA Astrophysics Data System (ADS)

Vessally, Esmail; Dehbandi, Behnam; Ahmadi, Elaheh

2016-09-01

Singlet-triplet energy differences in Arduengo-type carbenes XC2HN2C compared and contrasted with their sila, germa, stana and plumba analogues; at B3LYP/6-311++G** level of theory. Free Gibbs energy differences between triplet (t) and singlet (s) states (Δ G(t-s)) change in the following order: plumbylenes > stannylenes > germylenes > silylenes > carbenes. The singlet states in XC2HN2C are generally more stable when the electron withdrawing groups such as-F was used at β-position. However, the singlet states in XC2N2HM (M = Si, Ge, Sn, and Pb) are generally more stable when the withdrawing groups such as-F was placed. The puckering energy is investigated for each the singlet and triplet states. The DFT calculations found the linear correlation to size of the group 14 divalent element (M), the ∠N-M-N angle, and the Δ(LUMO-HOMO) of XC2HN2M.

48 CFR 14.303 - Modification or withdrawal of bids.

Code of Federal Regulations, 2013 CFR

2013-10-01

... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not be viewed and shall be purged from primary and backup data storage systems. [48 FR 42171, Sept. 19, 1983, as...

48 CFR 14.303 - Modification or withdrawal of bids.

Code of Federal Regulations, 2012 CFR

2012-10-01

... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not be viewed and shall be purged from primary and backup data storage systems. [48 FR 42171, Sept. 19, 1983, as...

48 CFR 14.303 - Modification or withdrawal of bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not be viewed and shall be purged from primary and backup data storage systems. [48 FR 42171, Sept. 19, 1983, as...

48 CFR 14.303 - Modification or withdrawal of bids.

Code of Federal Regulations, 2014 CFR

2014-10-01

... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not be viewed and shall be purged from primary and backup data storage systems. [48 FR 42171, Sept. 19, 1983, as...

48 CFR 14.303 - Modification or withdrawal of bids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not be viewed and shall be purged from primary and backup data storage systems. [48 FR 42171, Sept. 19, 1983, as...

Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study

PubMed Central

Hicks, Jacqueline D.; Hyde, Alan M.; Cuezva, Alberto Martinez; Buchwald, Stephen L.

2009-01-01

We report the efficient N-arylation of acyclic secondary amides and related nucleophiles with aryl nonaflates, triflates, and chlorides. This method allows for easy variation of the aromatic component in tertiary aryl amides. A new biaryl phosphine with P-bound 3,5-(bis)trifluoromethylphenyl groups was found to be uniquely effective for this amidation. The critical aspects of the ligand were explored through synthetic, mechanistic, and computational studies. Systematic variation of the ligand revealed the importance of (1) a methoxy group on the aromatic carbon of the “top ring” ortho to the phosphorus and (2) two highly electron-withdrawing P-bound 3,5-(bis)trifluoromethylphenyl groups. Computational studies suggest the electron-deficient nature of the ligand is important in facilitating amide binding to the LPd(II)(Ph)(X) intermediate. PMID:19886610

Antihistamine Pretreatment to Reduce Incidence of Withdrawal Movement After Rocuronium Injection

PubMed Central

Lee, Ho Jun; Han, Sung Jin; Kim, Heezoo; Lee, Il Ok; Kong, Myoung Hoon; Kim, Nan Suk; Lim, Sang Ho

2009-01-01

The purpose of this study was to determine the effectiveness of antihistamine therapy for withdrawal movements caused by rocuronium injection. One hundred seventy one ASA I-II adults undergoing elective surgery were randomly assigned to one of two groups. Patients in the control group (Group C) were premedicated with 2 mL normal saline, and those in the antihistamine group (Group A) were pre-medicated with 2 mL (45.5 mg) pheniramine maleate. After the administration of thiopental sodium 5 mg/kg, rocuronium 0.6 mg/kg was injected. Withdrawal movements were assessed using a four-grade scale. The administration of antihistamine reveals lower grade of withdrawal movement after rocuronium injection. PMID:19794987

Physical origins of weak H{sub 2} binding on carbon nanostructures: Insight from ab initio studies of chemically functionalized graphene nanoribbons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ulman, Kanchan; Bhaumik, Debarati; Wood, Brandon C.

2014-05-07

We have performed ab initio density functional theory calculations, incorporating London dispersion corrections, to study the absorption of molecular hydrogen on zigzag graphene nanoribbons whose edges have been functionalized by OH, NH{sub 2}, COOH, NO{sub 2}, or H{sub 2}PO{sub 3}. We find that hydrogen molecules always preferentially bind at or near the functionalized edge, and display induced dipole moments. Binding is generally enhanced by the presence of polar functional groups. The largest gains are observed for groups with oxygen lone pairs that can facilitate local charge reorganization, with the biggest single enhancement in adsorption energy found for “strong functionalization” bymore » H{sub 2}PO{sub 3} (115 meV/H{sub 2} versus 52 meV/H{sub 2} on bare graphene). We show that for binding on the “outer edge” near the functional group, the presence of the group can introduce appreciable contributions from Debye interactions and higher-order multipole electrostatic terms, in addition to the dominant London dispersion interactions. For those functional groups that contain the OH moiety, the adsorption energy is linearly proportional to the number of lone pairs on oxygen atoms. Mixed functionalization with two different functional groups on a graphene edge can also have a synergistic effect, particularly when electron-donating and electron-withdrawing groups are combined. For binding on the “inner edge” somewhat farther from the functional group, most of the binding again arises from London interactions; however, there is also significant charge redistribution in the π manifold, which directly reflects the electron donating or withdrawing capacity of the functional group. Our results offer insight into the specific origins of weak binding of gas molecules on graphene, and suggest that edge functionalization could perhaps be used in combination with other strategies to increase the uptake of hydrogen in graphene. They also have relevance for the storage of hydrogen in porous carbon materials, such as activated carbons.« less

[The effect of palonosetron on rocuronium-induced withdrawal movement].

PubMed

Park, Ki-Bum; Jeon, Younghoon; Yi, Junggu; Kim, Ji-Hyun; Chung, Seung-Yeon; Kwak, Kyung-Hwa

Rocuronium causes pain and withdrawal movement during induction of anesthesia. In this study, palonosetron was investigated to have analgesic effect on the reduction of rocuronium-induced withdrawal movement. 120 patients were randomly assigned to one of three groups to receive either saline, lidocaine 20mg, or palonosetron 0.075mg with a tourniquet applied two minutes before thiopental sodium (5mg.kg -1 ) was given intravenously. After loss of consciousness, rocuronium (0.6mg.kg -1 ) was injected and the withdrawal movement was estimated by 4-point scale in a double-blind manner. The overall incidence of rocuronium withdrawal movement was 50% with lidocaine (p=0.038), 38% with palonosetron (p=0.006) compared with 75% for saline. The incidence of no pain to mild pain was significantly lower in the lidocaine and palonosetron groups (85% and 92% respectively) than in the saline group (58%). However, there was no significant difference in withdrawal movement between the lidocaine and palonosetron groups. There was no severe movement with palonosetron. Pretreatment of palonosetron with venous occlusion may attenuate rocuronium-induced withdrawal movement as effective as the use of lidocaine. It suggested that peripheral action of palonosetron was effective to reduce rocuronium-induced withdrawal movement. Copyright © 2016. Publicado por Elsevier Editora Ltda.

Trajectories of Social Withdrawal from Grades 1 to 6: Prediction from Early Parenting, Attachment, and Temperament

ERIC Educational Resources Information Center

Booth-LaForce, Cathryn; Oxford, Monica L.

2008-01-01

From 1,092 children in the NICHD Study of Early Child Care and Youth Development, the authors identified 3 trajectory patterns of social withdrawal from teacher reports in Grades 1-6: a normative consistently low group (86%), a decreasing group (5%) with initially high withdrawal that decreased, and an increasing group (9%) with initially low…

Chemical structure-based predictive model for the oxidation of trace organic contaminants by sulfate radical.

PubMed

Ye, Tiantian; Wei, Zongsu; Spinney, Richard; Tang, Chong-Jian; Luo, Shuang; Xiao, Ruiyang; Dionysiou, Dionysios D

2017-06-01

Second-order rate constants [Formula: see text] for the reaction of sulfate radical anion (SO 4 •- ) with trace organic contaminants (TrOCs) are of scientific and practical importance for assessing their environmental fate and removal efficiency in water treatment systems. Here, we developed a chemical structure-based model for predicting [Formula: see text] using 32 molecular fragment descriptors, as this type of model provides a quick estimate at low computational cost. The model was constructed using the multiple linear regression (MLR) and artificial neural network (ANN) methods. The MLR method yielded adequate fit for the training set (R training 2 =0.88,n=75) and reasonable predictability for the validation set (R validation 2 =0.62,n=38). In contrast, the ANN method produced a more statistical robustness but rather poor predictability (R training 2 =0.99andR validation 2 =0.42). The reaction mechanisms of SO 4 •- reactivity with TrOCs were elucidated. Our result shows that the coefficients of functional groups reflect their electron donating/withdrawing characters. For example, electron donating groups typically exhibit positive coefficients, indicating enhanced SO 4 •- reactivity. Electron withdrawing groups exhibit negative values, indicating reduced reactivity. With its quick and accurate features, we applied this structure-based model to 55 discrete TrOCs culled from the Contaminant Candidate List 4, and quantitatively compared their removal efficiency with SO 4 •- and OH in the presence of environmental matrices. This high-throughput model helps prioritize TrOCs that are persistent to SO 4 •- based oxidation technologies at the screening level, and provide diagnostics of SO 4 •- reaction mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Substituted 2-benzothiazolamines as sodium flux inhibitors: quantitative structure-activity relationships and anticonvulsant activity.

PubMed

Hays, S J; Rice, M J; Ortwine, D F; Johnson, G; Schwarz, R D; Boyd, D K; Copeland, L F; Vartanian, M G; Boxer, P A

1994-10-01

Thirty-two aryl-substituted 2-benzothiazolamines have been tested for their ability to modulate sodium flux in rat cortical slices. A QSAR analysis, applied to these derivatives, showed a trend toward increasing potency as sodium flux inhibitors with increasing lipophilicity, decreasing size, and increasing electron withdrawal of the benzo ring substituents. Additionally, 4- or 5-substitution of the benzo ring was found to decrease potency. The combination of increased lipophilicity, small size, and electron withdrawal severely limited which groups were tolerated on the benzo ring, thus suggesting that the optimal substitution patterns have been prepared within this series. Nine of these compounds were potent inhibitors of veratridine-induced sodium flux (NaFl). These nine compounds also proved to be anticonvulsant in the maximal electroshock (MES) assay. Fourteen additional 2-benzothiazolamines demonstrated activity in the MES screen, yet exhibited no activity in the NaFl assay. These derivatives may be interacting at the sodium channel in a manner not discernible by the flux paradigm, or they may be acting by an alternative mechanism in vivo.

Function of CN group in organic sensitizers: The first principle study.

PubMed

Liu, Yun; Shao, Di; Bai, Xiaohui; Yang, Zhenqing; Lin, Chundan; Shao, Changjin

2017-05-15

The cyano group (CN) of the acceptor in organic sensitizers plays an important role for highly efficient dye-sensitized solar cells. In this paper, three 5, 6-difluoro-2,1,3-benzothiadiazole (DFBTD) organic molecules with different number of CN units, named ME15, ME16 and ME17, were investigated by the density functional theory (DFT) and time-dependent DFT (TDDFT). We analyzed the CNs effects on the electronic structures, optical properties, adsorption modes and electron transfer and injection. The result shows that ME17 has the largest maximum absorption wavelength (λ max ) among these new designed dyes due to the strong electron withdrawing ability of two CNs. In addition, CN greatly influence the adsorption modes of dye/TiO 2 and electron injection mechanism. ME16 with one CN also has good optical absorption properties and its acceptor has the strongest coupling strength with the TiO 2 semiconductor which is favorable for electron transfer and injection. Thus, we believe that the number of CN groups in acceptor should be moderate and one CN in D-A-π-A structure dyes may be the more appropriate focusing on the light harvesting ability, electron transfer and electron injection. Copyright © 2017 Elsevier B.V. All rights reserved.

An organoboron compound with a wide absorption spectrum for solar cell applications.

PubMed

Liu, Fangbin; Ding, Zicheng; Liu, Jun; Wang, Lixiang

2017-11-09

Organoboron compounds offer new approaches to tune the electronic structures of π-conjugated molecules. In this work, an electron acceptor (M-BNBP4P-1) is developed by endcapping an organoboron core unit with two strong electron-withdrawing groups. M-BNBP4P-1 exhibits a unique wide absorption spectrum with two strong absorption bands in the long wavelength region (λ max = 771 nm) and the short wavelength region (λ max = 502 nm), which indicate superior sunlight harvesting capability. This is due to its special electronic structure, i.e. a delocalized LUMO and a localized HOMO. Prototype solution-processed organic solar cells based on M-BNBP4P-1 show a power conversion efficiency of 7.06% and a wide photoresponse from 350 nm to 880 nm.

Process for preparing 2,3-dihydroxybenzoic acid amides of tetraazaalkanes and cycloalkanes

DOEpatents

Weitl, Frederick L.; Raymond, Kenneth N.

1985-01-01

A compound of the formula: ##STR1## wherein X is hydrogen or a conventional electron-withdrawing group, particularly --SO.sub.3 H or a salt thereof; n is 2, 3, or 4; m is 2, 3, or 4; and p is 2 or 3. The present compounds are useful as specific sequestering agents for actinide (IV) ions. Also described is a method for the 2,3-dihydroxybenzamidation of azaalkanes.

Tuning anion-functionalized ionic liquids for improved SO2 capture.

PubMed

Cui, Guokai; Zheng, Junjie; Luo, Xiaoyan; Lin, Wenjun; Ding, Fang; Li, Haoran; Wang, Congmin

2013-09-27

You can have your cake and eat it too: A "dual-tuning" strategy for improving the capture of SO2 was developed by introducing electron-withdrawing sites on the anions to produce several kinds of functionalized ionic liquids. Those functionalized with a halogen group exhibited improved performance over their non-halogenated counterparts, leading to highly efficient and reversible capture. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New Synthetic Approaches to TAT

DTIC Science & Technology

1990-03-30

stabilized externally by resonance stabilization of electron withdrawing substituents placed on all four Nitrogen aL,.ms (T,- N -:, ...7; 4- N -NO2 HMX, etc...or internally by ring carbonyl groups adja- cent to the ring- N -atoms (amide resonance). 1. Cyclization experiments on methylene-bisacetamide (MBA4...more, the high instability of the desired 8-membered [8]ane- N 4 system, and the difficulty to apply proper cond’tion-. what the final products can

Chemoselective N-heterocyclic carbene-catalyzed cross-benzoin reactions: importance of the fused ring in triazolium salts.

PubMed

Langdon, Steven M; Wilde, Myron M D; Thai, Karen; Gravel, Michel

2014-05-28

Morpholinone- and piperidinone-derived triazolium salts are shown to catalyze highly chemoselective cross-benzoin reactions between aliphatic and aromatic aldehydes. The reaction scope includes ortho-, meta-, and para-substituted benzaldehyde derivatives with a range of electron-donating and -withdrawing groups as well as branched and unbranched aliphatic aldehydes. Catalytic loadings as low as 5 mol % give excellent yields in these reactions (up to 99%).

Divergent Reactivity of Rhodium(I) Carbenes Derived from Indole Annulations.

PubMed

Li, Xiaoxun; Li, Hui; Song, Wangze; Tseng, Po-Sen; Liu, Lingyan; Guzei, Ilia A; Tang, Weiping

2015-10-26

Rhodium(I) carbenes were generated from propargylic alcohol derivatives as the result of a dehydrative indole annulation. Depending on the choice of the electron-withdrawing group on the aniline nitrogen nucleophile, either a cyclopropanation product or dimerization product was obtained chemoselectively. Intramolecular hydroamidation occurred for the same type of propargylic alcohol derivatives when other transition-metal catalysts were employed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cyclometalated ruthenium(II) complexes with a bis-carbene CCC-pincer ligand.

PubMed

Zhang, You-Ming; Shao, Jiang-Yang; Yao, Chang-Jiang; Zhong, Yu-Wu

2012-08-21

The first series of cyclometalated ruthenium complexes with a CCC-pincer bis-carbene ligand have been obtained as bench-stable compounds. Single-crystal X-ray analysis of one of these complexes with 4'-di-p-anisylamino-2,2':6',2''-terpyridine is presented. The Ru(II/III) redox potentials and MLCT absorptions of these complexes can be varied by attaching an electron-donating or -withdrawing group on the noncyclometalating ligand.

Effect of Nimodipine on Morphine-related Withdrawal Syndrome in Rat Model: An Observational Study

PubMed Central

Mishra, Pravash Ranjan; Barik, Mayadhar; Ray, Subrata Basu

2017-01-01

Objective: To observe the effect of L-type calcium channel blocker like nimodipine on morphine's withdrawal when it was administered continuously along with morphine versus a single bolus dose of nimodipine, which was administered at the end of the experiment before the precipitation of withdrawal reaction in morphine-dependent rats. Materials and Methods: Four groups of adult male Wistar rats were rendered morphine dependent by subcutaneous injections of morphine at a dose of 10 mg/kg for 10 days. Nimodipine 10 mg/kg intraperitoneally (ip) administered to one group once daily before morphine administration in the entire experimental period, and another group received nimodipine only once at the end of the experiment as a single bolus dose 2 mg/kg before the administration of naloxone. Naloxone 3 mg/kg was administered ip to all the groups to precipitate withdrawal reactions. The withdrawal reactions were evaluated and scored as per the Gellert and Holtzman global withdrawal rating scale. Results: Nimodipine when administered as a single bolus dose before naloxone administration in morphine-dependant rats reduced the features of withdrawal reactions more effectively than continuous administration of nimodipine along with morphine throughout the experimental period. Conclusion: We discovered that nimodipine helps in attenuating the severity of morphine withdrawal having potential role encountered during pharmacotherapy with morphine management of opioid dependence, well memory, impairement, cell signaling and phosphorylation of neuron. PMID:28553371

Effect of Nimodipine on Morphine-related Withdrawal Syndrome in Rat Model: An Observational Study.

PubMed

Mishra, Pravash Ranjan; Barik, Mayadhar; Ray, Subrata Basu

2017-01-01

To observe the effect of L-type calcium channel blocker like nimodipine on morphine's withdrawal when it was administered continuously along with morphine versus a single bolus dose of nimodipine, which was administered at the end of the experiment before the precipitation of withdrawal reaction in morphine-dependent rats. Four groups of adult male Wistar rats were rendered morphine dependent by subcutaneous injections of morphine at a dose of 10 mg/kg for 10 days. Nimodipine 10 mg/kg intraperitoneally (ip) administered to one group once daily before morphine administration in the entire experimental period, and another group received nimodipine only once at the end of the experiment as a single bolus dose 2 mg/kg before the administration of naloxone. Naloxone 3 mg/kg was administered ip to all the groups to precipitate withdrawal reactions. The withdrawal reactions were evaluated and scored as per the Gellert and Holtzman global withdrawal rating scale. Nimodipine when administered as a single bolus dose before naloxone administration in morphine-dependant rats reduced the features of withdrawal reactions more effectively than continuous administration of nimodipine along with morphine throughout the experimental period. We discovered that nimodipine helps in attenuating the severity of morphine withdrawal having potential role encountered during pharmacotherapy with morphine management of opioid dependence, well memory, impairement, cell signaling and phosphorylation of neuron.

Neighbouring group processes in the deamination of protonated phenylalanine derivatives.

PubMed

Lioe, Hadi; O'Hair, Richard A J

2005-10-21

The gas-phase fragmentation of protonated phenylalanine and a series of its derivatives (tyrosine, 4-methylphenylalanine, 4-aminophenylalanine, 4-methoxyphenylalanine, 4-tert-butylphenylalanine, 4-fluorophenylalanine, 4-chlorophenylalanine, 4-bromophenylalanine, 4-iodophenylalanine, 4-cyanophenylalanine, 4-nitrophenylalanine, 3-fluorophenylalanine, and 3,4-dichlorophenylalanine) were examined using a combination of low energy CID in a quadrupole ion trap mass spectrometer as well as DFT calculations and RRKM modelling. In particular, the relationship between the electron-donating ability of the substituent and the competitive losses of H2O + CO and NH3 were explored through the application of the Hammett equation. It was found that electron-donating substituents promote the loss of NH3, while electron-withdrawing substituents suppress the loss of NH3 and favour the H2O + CO loss fragmentation channel instead. These observations are consistent with a neighbouring group pathway operating for the loss of NH3. Molecular orbital calculation (at the B3LYP/6-31+G(d,p) level of theory) were also performed for a range of derivatives to compare the relative transition state energy barriers for three competing mechanisms: (i) the combined loss of H2O + CO, which is triggered by an initial intramolecular proton transfer from the ammonium group to hydroxyl OH, followed by the combined loss of H2O and CO to form an immonium ion; (ii) loss of NH3 via an aryl assisted neighbouring group pathway to yield a phenonium ion; (iii) loss of NH3 via a 1,2-hydride migration process, which results in the formation of a benzyl cation. The relative energy barriers for H2O + CO loss remain nearly constant, while that for both NH3 pathways increase as the substituent moves from electron-donating to electron-withdrawing. The relative transition state energy for loss of NH3 via the aryl assisted neighbouring group pathway is always lower than that of the 1,2-hydride migration process. RRKM modelling of the DFT predicted barrier heights suggest that the rate constants for H2O + CO loss are insensitive to the substituent on the ring, while the NH3 loss channels are greatly affected by the substituent. These theoretical results are consistent with the experimental observation of the relative yields of the competing fragmentation channels. Finally, comparisons with published gas phase and condensed phase studies on related systems are made.

Benzoin Radicals as Reducing Agent for Synthesizing Ultrathin Copper Nanowires.

PubMed

Cui, Fan; Dou, Letian; Yang, Qin; Yu, Yi; Niu, Zhiqiang; Sun, Yuchun; Liu, Hao; Dehestani, Ahmad; Schierle-Arndt, Kerstin; Yang, Peidong

2017-03-01

In this work, we report a new, general synthetic approach that uses heat driven benzoin radicals to grow ultrathin copper nanowires with tunable diameters. This is the first time carbon organic radicals have been used as a reducing agent in metal nanowire synthesis. In-situ temperature dependent electron paramagnetic resonance (EPR) spectroscopic studies show that the active reducing agent is the free radicals produced by benzoins under elevated temperature. Furthermore, the reducing power of benzoin can be readily tuned by symmetrically decorating functional groups on the two benzene rings. When the aromatic rings are modified with electron donating (withdrawing) groups, the reducing power is promoted (suppressed). The controllable reactivity gives the carbon organic radical great potential as a versatile reducing agent that can be generalized in other metallic nanowire syntheses.

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters--An Experimental and Theoretical Study on Directing Group Chemoselectivity.

PubMed

Devlin, Jennifer; Kerr, William J; Lindsay, David M; McCabe, Timothy J D; Reid, Marc; Tuttle, Tell

2015-06-25

Herein we report a combined experimental and theoretical study on the deuterium labelling of benzoate ester derivatives, utilizing our developed iridium N-heterocyclic carbene/phosphine catalysts. A range of benzoate esters were screened, including derivatives with electron-donating and -withdrawing groups in the para- position. The substrate scope, in terms of the alkoxy group, was studied and the nature of the catalyst counter-ion was shown to have a profound effect on the efficiency of isotope exchange. Finally, the observed chemoselectivity was rationalized by rate studies and theoretical calculations, and this insight was applied to the selective labelling of benzoate esters bearing a second directing group.

Comparison of cannabis and tobacco withdrawal: severity and contribution to relapse.

PubMed

Budney, Alan J; Vandrey, Ryan G; Hughes, John R; Thostenson, Jeff D; Bursac, Zoran

2008-12-01

This naturalistic telephone survey study compared perceptions of withdrawal severity in 67 daily cannabis users and 54 daily tobacco cigarette smokers who made quit attempts during the prior 30 days. A Withdrawal Symptom Checklist assessed the severity of abstinence symptoms and a Likert scale assessed perceived relations between abstinence symptoms and relapse. A composite Withdrawal Discomfort Score did not differ significantly between groups (M = 13.0 for cannabis, vs. M = 13.2 for tobacco). Individual symptom severity ratings were also of similar magnitude, except craving and sweating were slightly higher for tobacco. Both groups reported that withdrawal contributed substantially to relapse, and the strength of these ratings was similar across groups. The diverse convenience sample examined in this study adds external validity and generalizability to prior studies that included only users not planning to quit or excluded many common types of cannabis users. The comparable withdrawal experience from these heterogeneous cannabis and tobacco users supports previous findings from controlled laboratory studies and indicates that real-world, frequent cannabis users perceive that withdrawal symptoms negatively affect their desire and ability to quit.

Determination of adiabatic ionization potentials and electron affinities of energetic molecules with the Gaussian-4 method

NASA Astrophysics Data System (ADS)

Manaa, M. Riad

2017-06-01

Adiabatic ionization potentials (IPad) and electron affinities (EAad) are determined with the Gaussian-4 (G4) method for the energetic molecules PETN, RDX, β-δ-HMX, CL-17, TNB, TNT, CL-14, DADNE, TNA, and TATB. The IPad and EAad values are in the range of 8.43-11.73 and 0.74-2.86 eV, respectively. Variations are due to substitutional effects of electron withdrawing and donating functional groups. Enthalpies of formation are also determined for several of these molecules to augment the list of recently reported G4 values. The calculated IPad and EAad provide quantitative assessment of such molecular properties as chemical hardness, molecular electronegativity, and "intrinsic" molecular physical hardness.

Cultivating Fluorescent Flowers with Highly Luminescent Carbon Dots Fabricated by a Double Passivation Method.

PubMed

Han, Shuai; Chang, Tao; Zhao, Haiping; Du, Huanhuan; Liu, Shan; Wu, Baoshuang; Qin, Shenjun

2017-07-07

In this work, we present the fabrication of highly luminescent carbon dots (CDs) by a double passivation method with the assistance of Ca(OH)₂. In the reaction process, Ca 2+ protects the active functional groups from overconsumption during dehydration and carbonization, and the electron-withdrawing groups on the CD surface are converted to electron-donating groups by the hydroxyl ions. As a result, the fluorescence quantum yield of the CDs was found to increase with increasing Ca(OH)₂ content in the reaction process. A blue-shift optical spectrum of the CDs was also found with increasing Ca(OH)₂ content, which could be attributed to the increasing of the energy gaps for the CDs. The highly photoluminescent CDs obtained (quantum yield: 86%) were used to cultivate fluorescent carnations by a water culture method, while the results of fluorescence microscopy analysis indicated that the CDs had entered the plant tissue structure.

Computational Studies on Optoelectronic and Nonlinear Properties of Octaphyrin Derivatives

PubMed Central

Islam, Nasarul; Lone, Irfan H.

2017-01-01

The electronic and nonlinear optical (NLO) properties of octaphyrin derivatives were studied by employing the DFT/TDFT at CAM-B3LYP/6-311++G (2d, 2p) level of the theory. Thiophene, phenyl, methyl and cyano moieties were substituted on the molecular framework of octaphyrin core, in order to observe the change in optoelectronic and nonlinear response of these systems. The frontier molecular orbital studies and values of electron affinity reveals that the studied compounds are stable against the oxygen and moisture present in air. The calculated ionization energies, adiabatic electron affinity and reorganization energy values indicate that octaphyrin derivatives can be employed as effective n-type material for Organic Light Emitting Diodes (OLEDs). This character shows an enhancement with the introduction of an electron withdrawing group in the octaphyrin framework. The polarizability and hyperpolarizability values of octaphyrin derivatives demonstrate that they are good candidates for NLO devices. The nonlinear response of these systems shows enhancement on the introduction of electron donating groups on octaphyrin moiety. However, these claims needs further experimental verification. PMID:28321394

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

PubMed Central

Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

2013-01-01

Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (p<0.05) among groups in both phases; the 200 mg group received the least amount in Phase 1, and the 600 mg group received the most in both phases. In Phase 1, tramadol 200 mg produced significantly lower peak ratings than placebo on ratings of insomnia, lacrimation, muscular tension, and sneezing. Only tramadol 600 mg produced miosis in Phase 1. In Phase 2, tramadol 600 mg produced higher peak ratings of rhinorrhea, irritable, depressed, heavy/sluggish, and hot/cold flashes than placebo. There were no serious adverse events and no signal of abuse liability for tramadol. Conclusions ER tramadol 200 mg modestly attenuated opioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

Laser Induced Polymerization Reactions in Solid Propellant Binders.

DTIC Science & Technology

1982-06-18

were -then evacuated in a glass vacuum desiccatbr to remove dissolved air and then opened to the atmosphere. Some samples were run under a nitrogen or...diacetate solution was prepared using acetonitrile as solvent. Molar absorbtivities at 266 and 355 nm for l,l’-ferrocenedicarboxylic acid were obtained with...increasing order of the electron withdrawing ability of the groups attached to the ferrocene ring. The order is as shown. r l,l’-Ferrocenedicarboxylic Acid

Catalytic trimerization of aromatic nitriles for synthesis of polyimide matrix resins

NASA Technical Reports Server (NTRS)

Hsu, L. C.

1974-01-01

Aromatic nitriles may be trimerized at moderate temperature and pressure with p-toluenesulfonic acid as catalyst. Studies were conducted to establish the effect of the reaction temperature, pressure, time, and catalyst concentration on yield of the trimerized product. Trimerization studies were also conducted to establish the effect of substituting electron donating or withdrawing groups on benzonitrile. Preliminary results of using the catalytic trimerization approach to prepare s-triazine cross-linked polyimide/graphite fiber composites are presented.

Effects of the capping ligands, linkers and oxide surface on the electron injection mechanism of copper sulfide quantum dot-sensitized solar cells.

PubMed

Suárez, Javier Amaya; Plata, Jose J; Márquez, Antonio M; Sanz, Javier Fdez

2017-06-07

Quantum dot-sensitized solar cells, QDSCs, are a clean and effective alternative to fossil fuels to reduce CO 2 emissions. However, the different components that constitute the QDSCs and the difficulty of isolating experimentally their effects on the performance of the whole system slow down the development of more efficient devices. In this work, DFT calculations are combined with a bottom-up approach to differentiate the effect of each component on the electronic structure and absorption spectra. First, Cu 2 S QDs were built including a U parameter to effectively describe the localization of electrons. The effect of capping agents is addressed using ligands with different electron-donating/withdrawing groups. The role of linkers and their adsorption on the oxide surface are also examined. Finally, we propose a main indirect electron injection mechanism based on the position of the peaks of the spectra.

Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial

PubMed Central

Lähteenmäki, Ritva; Puustinen, Juha; Vahlberg, Tero; Lyles, Alan; Neuvonen, Pertti J; Partinen, Markku; Räihä, Ismo; Kivelä, Sirkka-Liisa

2014-01-01

Aim We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here ‘BZD’) use. Methods A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6 months were noted. Results There were two drop-outs on CRM and one on placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025). Withdrawal symptoms did not differ between the groups. Conclusions Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo. PMID:24286360

Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease.

PubMed

Kwon, Hyemi; Kim, Won Gu; Jang, Eun Kyung; Kim, Mijin; Park, Suyeon; Jeon, Min Ji; Kim, Tae Yong; Ryu, Jin Sook; Shong, Young Kee; Kim, Won Bae

2016-06-01

Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse. This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal. Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%. TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease

PubMed Central

Kwon, Hyemi; Jang, Eun Kyung; Kim, Mijin; Park, Suyeon; Jeon, Min Ji; Kim, Tae Yong; Ryu, Jin-Sook; Shong, Young Kee; Kim, Won Bae

2016-01-01

Background Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse. Methods This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal. Results Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%. Conclusion TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease. PMID:27118279

Influence of functional groups on the photophysical properties of dimethylamino chalcones as laser dyes

NASA Astrophysics Data System (ADS)

Ibnaouf, K. H.; Elzupir, A. O.; AlSalhi, M. S.; Alaamer, Abdulaziz S.

2018-02-01

In this report, a series of 3-(4-(Dimethylamino) phenyl)-1-(4,3 di-substituted phenyl)-(2E) - propen -1-one chalcones was synthesised and examined as optical materials. The influence of functional groups (FG) and solvents on their photophysical properties was investigated. These include absorption, fluorescence, Stokes shift, and amplified spontaneous emission (ASE). The absorption spectra of all compounds showed a wavelength band in the range 404-429 nm, whereas the fluorescence spectra exhibited a band at 470-535 nm. We found that the fluorescence intensity was inversely proportional to the concentration of chalcones. The FGs and solvents had an amazing effect on the photophysical properties of the synthesised materials. Unexpectedly, the electron withdrawing group showed a highly red shift, whereas the electron donating group exhibited a blue shift. Further, these compounds showed large Stokes shifts (up to 5800 cm-1). ASE was observed under pump pulse laser excitation, and the wavelengths were tuned from 509 to 566 nm.

Remifentanil Prevents Withdrawal Movements Caused by Intravenous Injection of Rocuronium

PubMed Central

Choi, Byung In; Choi, Seung Ho; Shin, Yang-Sik; Lee, Sung Jin; Yoon, Kyung Bong; Shin, Seo Kyung

2008-01-01

Purpose The incidence of pain induced withdrawal movement following intravenous injection of rocuronium is high. This randomized, double-blind, placebo-controlled study was designed to evaluate the effect of pretreatment of remifentanil on the withdrawal movements due to intravenous injection of rocuronium during anesthetic induction. Materials and Methods Ninety adult female patients undergoing thyroidectomy were randomly allocated to three groups. Each patient intravenously received one of three solutions of equal volume (4 mL): normal saline (Group I, n = 30), 0.5 µg/kg remifentanil (Group II, n = 30) or 1 µg/kg remifentanil (Group III, n = 30). Thirty seconds after remifentanil administration, anesthesia was induced with 5 mg/kg IV thiopental. Twenty seconds after thiopental injection, 0.6 mg/kg IV rocuronium was administered (injection rate of 0.5 mL/sec) and patients' withdrawal movements were assessed. Mean arterial pressure (MAP) and heart rate were assessed on arrival in the operation room, before the tracheal intubation and immediately, 1 and 2 min after the tracheal intubation. Results The incidence of withdrawal movements was significantly lower in both of the remifentanil groups (3 and 0% in Group II and III, respectively) than in the saline group (70%). Remifentanil attenuated the increase of heart rate and MAP immediately and 1 min after the tracheal intubation. Conclusion The pretreatment with 0.5 and 1.0 µg/kg remifentanil of bolus doses prevented the withdrawal movements caused by rocuronium injection, and effectively blunted cardiovascular activation following tracheal intubation. PMID:18452256

Taurine restores the exploratory behavior following alcohol withdrawal and decreases BDNF mRNA expression in the frontal cortex of chronic alcohol-treated rats.

PubMed

Hansen, Alana Witt; Almeida, Felipe Borges; Bandiera, Solange; Pulcinelli, Rianne Remus; Fragoso, Ana Luiza Rodrigues; Schneider, Ricardo; Barros, Helena Maria Tannhauser; Gomez, Rosane

2017-10-01

Alcohol use disorder is an alarming health problem, and the withdrawal symptoms increase the risk of relapse. We have hypothesized that taurine, a multitarget substance acting as a gamma-aminobutyric acid A receptor (GABA A R) positive modulator and a partial inhibitor of N-methyl-d-aspartate (NMDA) glutamate receptors, may reduce the withdrawal symptoms or modify behaviors when combined with alcohol. Therefore, we investigated the effects of taurine on behavior in the open field test (OFT), the GABA A R α 2 subunit and BDNF mRNA expression in the frontal cortex of rats after chronic alcohol treatment or upon withdrawal. Rats received alcohol 2g/kg (alcohol and withdrawal groups) or water (control group) twice daily by oral gavage for 28days. On day 29, the withdrawal rats received water instead of alcohol, and all groups were reallocated to receive 100mg/kg taurine or vehicle intraperitoneally, once a day for 5days. On day 33, the rats were exposed to OFT; 18h later, they were euthanized, and the frontal cortex was dissected for GABA A R α 2 subunit detection and BDNF mRNA expression determination by real-time quantitative PCR. Taurine administration restored rearing behavior to the control levels in the withdrawal rats. Taurine also showed anxiolytic-like effects in control rats and did not change the behaviors in the chronic alcohol group. Chronic alcohol treatment or withdrawal did not change the GABA A R α 2 subunit or BDNF mRNA expression in the frontal cortex, but taurine decreased the α 2 subunit level in control rats and to the BDNF levels in the alcohol rat group. We conclude that taurine restored exploratory behavior after alcohol withdrawal but that this effect was not related to the GABA A R α 2 subunit or BDNF mRNA expression in the frontal cortex of the rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute effects of a guided relaxation routine (body scan) on tobacco withdrawal symptoms and cravings in abstinent smokers.

PubMed

Cropley, Mark; Ussher, Michael; Charitou, Elli

2007-06-01

To examine the acute effects of a guided relaxation routine (body scan) on desire to smoke and tobacco withdrawal symptoms in overnight abstinent smokers. Experimental. Thirty individuals reporting to smoke 10 or more cigarettes daily for at least 3 years. Participants were assigned randomly to complete a 10-minute body scan (experimental group n = 15) or listen to a natural history passage for 10 minutes (control group n = 15). Ratings of strength of desire to smoke and smoking withdrawal symptoms were assessed at baseline, immediately after the interventions, and 5, 10 and 15 minutes post-intervention. There was a significant group x time interaction for strength of desire to smoke. The mean desire to smoke rating was significantly lower in the body scan group relative to the control group immediately after the intervention, and 5 minutes post-intervention. The body scan group also reported lower ratings of irritability, tension and restlessness, relative to the controls. A brief body scan intervention reduces strength of desire to smoke and some tobacco withdrawal symptoms in temporarily abstaining smokers. The body scan may be beneficial as a technique for managing cigarette cravings and withdrawal.

Nucleophilic fluorination of aromatic compounds

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R

2014-03-18

Iodylbenzene derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are used as precursors in aromatic nucleophilic substitution reactions. The iodyl group (IO.sub.2) is regiospecifically substituted by nucleophilic fluoride to provide the corresponding fluoroaryl derivatives. No-carrier-added [F-18]fluoride ion derived from anhydrous [F-18](F/Kryptofix, [F-18]CsF or a quaternary ammonium fluoride (e.g., Me.sub.4NF, Et.sub.4NF, n-Bu.sub.4NF, (PhCH.sub.2).sub.4NF) exclusively substitutes the iodyl moiety in these derivatives and provides high specific activity F-18 labeled fluoroaryl analogs. Iodyl derivatives of a benzothiazole analog and 6-iodyl-L-dopa derivatives have been synthesized as precursors and have been used in the preparation of no-carrier-added [F-18]fluorobenzothiazole as well as 6-[F-18]fluoro-L-dopa.

Use of fluorogestone acetate sponges or controlled internal drug release for estrus synchronization in ewes: Effects of hormonal profiles and reproductive performance.

PubMed

Swelum, Ayman Abdel-Aziz; Alowaimer, Abdullah Nasser; Abouheif, Mohamed Ahmed

2015-09-01

This study was carried out using 300 multiparous Najdi ewes during breeding season to compare the effects of fluorogestone acetate (FGA) sponges and controlled internal drug release (CIDR) dispensers to synchronize estrus on reproductive performance and hormonal profiles. Ewes were equally and randomly allotted into group A (FGA) and group B (CIDR); intravaginal progestagen was administered for 14-day period with intramuscular administration of 600-IU eCG at withdrawal time. Estrus was detected using a vasectomized ram starting 12 hours after progestagen withdrawal and repeated every 12 hours up to 84 hours. Blood samples were collected at the time of progestagen withdrawal (0 hour), 24 hours, and 48 hours. Follicle-stimulating hormone, LH, estradiol, and progesterone serum concentrations were measured using commercial ELISA kits and microtitrimetric plates. Timed laparoscopic insemination was performed 48 hours after progestagen withdrawal. Pregnancy and the number of fetuses were diagnosed by ultrasonography on Day 23 after insemination and confirmed on Days 35 and 60. The results revealed that the retention, vaginal discharge, and drawstring breakage rates after progestagen removal were significantly (P ≤ 0.05) higher in the FGA group (94.00, 98.58, and 9.22, respectively) than those in the CIDR group. On the other hand, pregnancy, fertility, twinning rates, and fecundity were significantly (P ≤ 0.05) higher in the CIDR group (77.86, 75.57, 34.34, and 1.02, respectively) than in the FGA group. Estrus responses in FGA and CIDR groups increased gradually to attain their significantly (P ≤ 0.05) higher percentages after 48 hours of progestagen withdrawal (91.49 and 92.37, respectively); thereafter, they decreased. The overall estrus responses and prolificacy did not differ between the FGA and CIDR groups. Follicle-stimulating hormone was significantly higher in the FGA group at 24 and 48 hours after progestagen withdrawal, whereas LH was significantly higher in the CIDR group at 48 hours after progestagen withdrawal. Estradiol and progesterone were significantly higher in the CIDR group at 0, 24, and 48 hours after progestagen withdrawal. These results indicated that although FGA and CIDR devices are efficient in synchronizing estrus in ewes, CIDR provided higher pregnancy, fertility, twinning rates, and fecundity than FGA. Copyright © 2015 Elsevier Inc. All rights reserved.

[A randomized, double-blind, controlled study: Ji-Tai tablet for the treatment of acute withdrawl syndrome of mild heroin dependence].

PubMed

Wang, Yuhong; Tang, Cuiqing; Cheng, Shuang; Cui, Guimei; Zhang, Ruiling; Zhang, Zhiyong; Xie, Lingyin; Lin, Yongxiong; Hao, Wei

2015-02-01

To investigate the efficacy and safety of Ji-Tai tablet and Ji-Tai tablet combined with buprenorphine in the treatment of patients with acute withdrawal syndrome of mild heroin dependence. A total of 150 patients with mild heroin dependence were recruited, and were randomly assigned to a Ji-Tai tablet group (n=50), a Ji-Tai tablet combined with buprenorphine group (n=50) and a control group (n=50) during a 10-day clinical trial. Opiate withdrawal scale (OWS) was used to measure the severity of withdrawal symptoms. Anxiety symptoms assessments were made at 0 day (baseline), the day 5 (middle), and the day 10 (end) by the Hamilton anxiety scale (HAMA). Symptoms were assessed before and 1 h or 2 h after medication each day. The total withdrawal symptoms scores and the daily reduction rate were used to measure the effect of Ji-Tai tablet vs Ji- Tai tablet plus buprenorphine. Safety evaluation was carried out by the following measures: baseline of treatment, drug side effects after the treatment, vital signs (blood pressure, heart rate, and respiration rate), laboratory examination (routine blood and urine tests and the liver and kidney function tests), and electrocardiograms. A total of 142 mild heroin dependence patients performed the experiments (including 48 in the Ji-Tai tablet group, 48 in the Ji-Tai tablet with buprenorphine group and 46 in the control group). The scores of baseline withdrawal symptoms were 43.520±19.786, 42.640±17.648 and 47.100±24.450, respectively, with no significant differences among the 3 groups (all P>0.05 ). During the 10-day treatment, the reduction rate of acute withdrawal symptoms scores increased daily, the acute withdrawal syndrome scores and the anxiety symptoms scores declined from day 0 to day 10, there was also no significant difference among the 3 groups (all P>0.05). Ji-Tai tablet did not affect vital signs such as blood pressure, heart rate, and respiration rate. Ji-Tai tablet or Ji-Tai tablet combined with buprenorphine had no effect on acute withdrawal symptoms of mild heroin dependence.

42 CFR 412.273 - Withdrawing an application, terminating an approved 3-year reclassification, or canceling a...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 3-year reclassification, or canceling a previous withdrawal or termination. 412.273 Section 412.273...-year reclassification, or canceling a previous withdrawal or termination. (a) Definitions. For purposes... to the provisions of this section, a hospital (or group of hospitals) may cancel a withdrawal or...

Social Withdrawal and Maladjustment in a Very Group-Oriented Society

ERIC Educational Resources Information Center

Valdivia, Ibis Alvarez; Schneider, Barry H.; Chavez, Kenia Lorenzo; Chen, Xinyin

2005-01-01

Elementary-school children in Cuba and Canada participated in measures of loneliness, sociometric status, friendship, aggression, and social withdrawal. Withdrawal was associated with loneliness in the Cuban data from both cohorts, Grade 4 and Grade 6. In the Canadian data, withdrawal was only linked to loneliness in Grade 6. In contrast with…

2,3-Dihydroxybenzoic acid amides of tetraazaalkanes and tetaaza cycloalkanes

DOEpatents

Weitl, F.L.; Raymond, K.N.

1980-01-01

This disclosure is directed to a compound of the formula given in the patent wherein X is hydrogen or a conventional electron-withdrawing group, particularly --SO[sub 3]H or a salt thereof; n is 2, 3, or 4; m is 2, 3, or 4; and p is 2 or 3. The present compounds are useful as specific sequestering agents for actinide (IV) ions. Also described is a method for the 2,3-dihydroxybenzamidation of azaalkanes. No Drawings

Breast Tumor pH: Design, Evaluation, and Application of Novel Reporter Molecules

DTIC Science & Technology

2001-10-01

DM, Burton DJ. J. Am Chem Soc. 1986, 108, 832. 8. Urata , H, Fuchikami T. Tet. Letters 1991,91. 9. Mehta, VD, Kulkarni PV, Mason RP, et al. 6...substitution reaction on an aryl iodide with trifluoromethyl copper ("CuCF3") [7]. Urata [8] described a convenient method for the in situ generation of...the stronger electron-withdrawing nature of the CF3 group causes this marked increase in acidity, which makes 6-CF3POL a better probe for

Insight into the kinetics and thermodynamics of the hydride transfer reactions between quinones and lumiflavin: a density functional theory study.

PubMed

Reinhardt, Clorice R; Jaglinski, Tanner C; Kastenschmidt, Ashly M; Song, Eun H; Gross, Adam K; Krause, Alyssa J; Gollmar, Jonathan M; Meise, Kristin J; Stenerson, Zachary S; Weibel, Tyler J; Dison, Andrew; Finnegan, Mackenzie R; Griesi, Daniel S; Heltne, Michael D; Hughes, Tom G; Hunt, Connor D; Jansen, Kayla A; Xiong, Adam H; Hati, Sanchita; Bhattacharyya, Sudeep

2016-09-01

The kinetics and equilibrium of the hydride transfer reaction between lumiflavin and a number of substituted quinones was studied using density functional theory. The impact of electron withdrawing/donating substituents on the redox potentials of quinones was studied. In addition, the role of these substituents on the kinetics of the hydride transfer reaction with lumiflavin was investigated in detail under the transition state (TS) theory assumption. The hydride transfer reactions were found to be more favorable for an electron-withdrawing substituent. The activation barrier exhibited a quadratic relationship with the driving force of these reactions as derived under the formalism of modified Marcus theory. The present study found a significant extent of electron delocalization in the TS that is stabilized by enhanced electrostatic, polarization, and exchange interactions. Analysis of geometry, bond-orders, and energetics revealed a predominant parallel (Leffler-Hammond) effect on the TS. Closer scrutiny reveals that electron-withdrawing substituents, although located on the acceptor ring, reduce the N-H bond order of the donor fragment in the precursor complex. Carried out in the gas-phase, this is the first ever report of a theoretical study of flavin's hydride transfer reactions with quinones, providing an unfiltered view of the electronic effect on the nuclear reorganization of donor-acceptor complexes.

Synthesis of inulin derivatives with quaternary phosphonium salts and their antifungal activity.

PubMed

Chen, Yuan; Tan, Wenqiang; Li, Qing; Dong, Fang; Gu, Guodong; Guo, Zhanyong

2018-07-01

Inulin is a kind of renewable and biodegradable carbohydrate with good water solubility and numerous physiological functions. For further utilization of inulin, chemical modification can be applied to improve its bioactivities. In this paper, five novel inulin derivatives were synthesized via chemical modification with quaternary phosphonium salt. Their antifungal activity against three kinds of plant pathogens including Colletotrichum lagenarium, Phomopsis asparagi, and Fusarium oxysporum was assessed with radial growth assay in vitro. Results revealed that all the inulin derivatives exhibited improved antifungal activity compared with inulin. Particularly, inulin modified with triphenylphosphine (TPhPAIL) exhibited the best antifungal activity with inhibitory indices of 80.0%, 78.8%, and 87.4% against Colletotrichum lagenarium, Phomopsis asparagi, and Fusarium oxysporum at 1.0mg/mL respectively. The results clearly showed that chemical modification of inulin with quaternary phosphonium salt could efficiently improve derivatives' antifungal activity. Further analysis of results indicated that the antifungal activity was influenced by alkyl chain length or electron-withdrawing ability of the grafted quaternary phosphonium salts. Longer alkyl chain lengths or the stronger electron-withdrawing groups would lead to enhanced antifungal efficacy. Copyright © 2018 Elsevier B.V. All rights reserved.

Prospective Randomized Trial Comparing Embryo Transfers of Cases with and without Catheter Rotation during Its Withdrawal.

PubMed

Yayla Abide, Cigdem; Ozkaya, Enis; Sanverdi, Ilhan; Bostancı Ergen, Evrim; Kurek Eken, Meryem; Devranoglu, Belgin; Bilgiç, Bulent Emre; Kilicci, Cetin; Kayatas Eser, Semra

2018-05-14

To compare embryo transfer (ET) technique based on catheter rotation during its withdrawal in cases with unexplained infertility in a prospective, randomized trial (NCT03097042). Two hundred intracytoplasmic sperm injection (ICSI) patients undergoing ET with cleaving or blastocyst-stage fresh embryos were randomized into 2 groups: cases with (n = 100), and without (n = 100) catheter rotation during its withdrawal. Groups were matched for age and some clinical parameters. A soft catheter was used to transfer a single embryo with catheter rotation during its withdrawal in the study group and without rotation in the control. The use of a stiff catheter or tenaculum was not needed in any case. Groups were compared in terms of cycle characteristics and clinical pregnancy rates. Pregnancy rate was significantly higher in the study group (41 vs. 26%, p = 0.04). Clinical pregnancy rate was also significantly higher in the study group (39 vs. 25%, OR 1.9 [1.1-3.5], p = 0.05). On the other hand, the ongoing pregnancy rate was similar between the 2 groups (33 vs. 23%, p = 0.2). Catheter rotation during its withdrawal may be associated with increased pregnancy and clinical pregnancy rates; however, the difference in ongoing pregnancy rates did not reach statistical significance. © 2018 S. Karger AG, Basel.

Comparison of the characteristics of long-term users of electronic cigarettes versus nicotine replacement therapy: A cross-sectional survey of English ex-smokers and current smokers.

PubMed

Nelson, Victoria A; Goniewicz, Maciej L; Beard, Emma; Brown, Jamie; Sheals, Kate; West, Robert; Shahab, Lion

2015-08-01

Electronic cigarettes (ECs) and nicotine replacement therapy (NRT) are non-combustible nicotine delivery devices being widely used as a partial or a complete long-term substitute for smoking. Little is known about the characteristics of long-term users, their smoking behaviour, attachment to smoking, experience of nicotine withdrawal symptoms, or their views on these devices. This study aimed to provide preliminary evidence on this and compare users of the different products. UK participants were recruited from four naturally occurring groups of long-term (≥6 months) users of either EC or NRT who had stopped or continued to smoke (N=36 per group, total N=144). Participants completed a questionnaire assessing socio-demographic and smoking characteristics, nicotine withdrawal symptoms, smoker identity and attitudes towards the products they were using. Adjusting for relevant confounders, EC use was associated with a stronger smoker identity (Wald X(2)(1)=3.9, p=0.048) and greater product endorsement (Wald X(2)(1)=4.6, p=0.024) than NRT use, irrespective of smoking status. Among ex-smokers, EC users reported less severe mood and physical symptoms (Wald X(2)(1)=6.1, p=0.014) and cravings (Wald X(2)(1)=8.5, p=0.003), higher perceived helpfulness of the product (Wald X(2)(1)=4.8, p=0.028) and lower intentions to stop using the product (Wald X(2)(1)=17.6, p<0.001) than NRT users. Compared with people who use NRT for at least 6 months, those who use EC over that time period appear to have a stronger smoker identity and like their products more. Among long-term users who have stopped smoking, ECs are perceived as more helpful than NRT, appear more effective in controlling withdrawal symptoms and continued use may be more likely. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

DFT studies on the ligand effect on electronic and optical properties of three series of functionalized Ir(III) complexes

NASA Astrophysics Data System (ADS)

Liu, Shujie; Li, Yangen; Hu, Xiaoying; Liu, Xiangdong; Guan, Bo

2018-01-01

With the help of DFT and TDDFT, a series of functionalized mononuclear iridium (III) complexes were systematically investigated to make clear the effect of auxiliary ligands on their electrionic and photophysical properties. It can be found that introducing electron withdrawing group (sbnd CF3) on benzene moiety can stabilize HOMO level, thus leading to wider HOMO-LUMO gap and blue shift in spectrum. More importantly, introducing sbnd CF3 on benzene moiety can also significantly improve the radiative decay rate (kr). On the other hand, the incorporation of electron donating groups (such as -Ph(CH3)3) into pyridine moiety on ligand reduce kr. The complexes 1c-3c and 1d-3d have improved charge balance ability and larger percentage of metal character. The results revealed the nature of the different substituents have a significant effect on the HOMO, LUMO energy levels and kr, resulting in the change of emission color and the quantum efficiency (Φp).

Tandem catalysis by palladium nanoclusters encapsulated in metal–organic frameworks

DOE PAGES

Li, Xinle; Guo, Zhiyong; Xiao, Chaoxian; ...

2014-08-25

A bifunctional Zr-MOF catalyst containing palladium nanoclusters (NCs) has been developed. The formation of Pd NCs was confirmed by transmission electron microscopy (TEM) and extended X-ray absorption fine structure (EXAFS). Combining the oxidation activity of Pd NCs and the acetalization activity of the Lewis acid sites in UiO-66-NH 2, this catalyst (Pd@UiO-66-NH 2) exhibits excellent catalytic activity and selectivity in a one-pot tandem oxidation-acetalization reaction. This catalyst shows 99.9% selectivity to benzaldehyde ethylene acetal in the tandem reaction of benzyl alcohol and ethylene glycol at 99.9% conversion of benzyl alcohol. We also examined various substituted benzyl alcohols and found thatmore » alcohols with electron-donating groups showed better conversion and selectivity compared to those with electron-withdrawing groups. As a result, we further proved that there was no leaching of active catalytic species during the reaction and the catalyst can be recycled at least five times without significant deactivation.« less

Design, Synthesis, Structural and Spectroscopic Studies of Push-Pull Two-Photon Absorbing Chromophores with Acceptor Groups of Varying Strength

PubMed Central

Morales, Alma R.; Frazer, Andrew; Woodward, Adam W.; Ahn-White, Hyo-Yang; Fonari, Alexandr; Tongwa, Paul; Timofeeva, Tatiana; Belfield, Kevin D.

2013-01-01

A new series of unsymmetrical diphenylaminofluorene-based chromophores with various strong π-electron acceptors were synthesized and fully characterized. The systematic alteration of the structural design facilitated the investigation of effects such as molecular symmetry and strength of electron-donating and/or withdrawing termini have on optical nonlinearity. In order to determine the electronic and geometrical properties of the novel compounds, a thorough investigation was carried out by a combination of linear and nonlinear spectroscopic techniques, single crystal X-ray diffraction, and quantum chemical calculations. Finally, on the basis of two-photon absorption (2PA) cross sections, the general trend for π -electron accepting ability, i.e., ability to accept charge transfer from diphenylamine was: 2-pyran-4-ylidene malononitrile (pyranone) > dicyanovinyl > bis(dicyanomethylidene)indane > 1-(thiophen-2-yl)propenone > dicyanoethylenyl > 3-(thiophen-2-yl)propenone. An analog with the 2-pyran-4-ylidene malononitrile acceptor group exhibited a nearly three-fold enhancement of the 2PA< δ (1650 GM at 840 nm), relative to other members of the series. PMID:23305555

The effect of environmental factors on morphine withdrawal in C57BL/6J mice: running wheel access and group housing.

PubMed

Balter, Rebecca E; Dykstra, Linda A

2012-11-01

There is evidence to suggest that the rewarding effects of drugs of abuse can be altered by environmental manipulations such as housing conditions and access to running wheels. There is less information about how these environmental manipulations alter withdrawal behaviors following the termination of chronic drug administration. The objective of this study is to examine the effects of access to running wheels and group housing on spontaneous morphine withdrawal. C57BL/6J mice were assigned to one of the three housing conditions: wheel access (singly housed), no wheels (singly housed), or group-housed (no wheels). Mice received 30 or 56 mg/kg morphine or saline (s.c.) twice daily for 5.5 days. At baseline and at 8, 24, 32, and 48 h following the final injection, latency to respond on a hot plate was determined across a range of temperatures (50, 52, 54, and 56 °C). Latency to respond decreased as a function of temperature. Response latencies during the withdrawal period were decreased in mice without wheel access treated with both 30 and 56 mg/kg of morphine. This increase in thermal sensitivity was significantly attenuated in singly housed mice with wheel access and in group-housed mice; however, the effects were less pronounced in the group-housed mice and depended upon the time during withdrawal. Both wheel access and group housing attenuate the increase in thermal sensitivity seen in morphine-treated mice during morphine withdrawal.

Acenes, Heteroacenes and Analogous Molecules for Organic Photovoltaic and Field Effect Transistor Applications

NASA Astrophysics Data System (ADS)

Granger, Devin Benjamin

Polycyclic aromatic hydrocarbons composed of benzenoid rings fused in a linear fashion comprise the class of compounds known as acenes. The structures containing three to six ring fusions are brightly colored and possess band gaps and charge transport efficiencies sufficient for semiconductor applications. These molecules have been investigated throughout the past several decades to assess their optoelectronic properties. The absorption, emission and charge transport properties of this series of molecules has been studied extensively to elucidate structure-property relationships. A wide variety of analogous molecules, incorporating heterocycles in place of benzenoid rings, demonstrate similar properties to the parent compounds and have likewise been investigated. Functionalization of acene compounds by placement of groups around the molecule affects the way in which molecules interact in the solid state, in addition to the energetics of the molecule. The use of electron donating or electron withdrawing groups affects the frontier molecular orbitals and thus affects the optical and electronic gaps of the molecules. The use of bulky side groups such as alkylsilylethynyl groups allows for crystal engineering of molecular aggregates, and changing the volume and dimensions of the alkylsilyl groups affects the intermolecular interactions and thus changes the packing motif. In chapter 2, a series of tetracene and pentacene molecules with strongly electron withdrawing groups is described. The investigation focuses on the change in energetics of the frontier molecular orbitals between the base acene and the nitrile and dicyanovinyl derivatives as well as the differences between the pentacene and tetracene molecules. The differences in close packing motifs through use of bulky alkylsilylethynyl groups is also discussed in relation to electron acceptor material design and bulk heterojunction organic photovoltaic characteristics. Chapter 3 focuses on molecular acceptor and donor molecules for bulk heterojunction organic photovoltaics based on anthrathiophene and benzo[1,2-b:4,5-b']dithiophene central units like literature molecules containing fluorene and dithieno[2,3-b:2',3'-d]silole cores. The synthetic strategies of developing reduced symmetry benzo[1,2-b:4,5-b']dithiophene to study the effect of substitution around the central unit is also described. The optical and electronic properties of the donors and acceptors are described along with the performance and characteristics of devices employing these molecules. The final two data chapters focus on new nitrogen containing polycyclic hydrocarbons containing indolizine and (2.2.2) cyclazine units. The optical, electronic and other physical properties of these molecules are explored, in addition to the synthetic strategies for incorporating the indolizine and cyclazine units. By use of alkylsilylethynyl groups, crystal engineering was investigated for the benzo[2,3-b:5,6-b']diindolizine chromophore described in chapter 4 to target the 2-D "brick-work" packing motif for application in field effect transistor devices. Optical and electronic properties of the cyclazine end-capped acene molecules described in chapter 5 were investigated and described in relation to the base acene molecules. In both cases, density functional theory calculations were conducted to better understand unexpected optical properties of these molecules, which are like the linear acene series despite the non-linear attachment.

Synthesis, characterization and nonlinear optical properties of symmetrically substituted dibenzylideneacetone derivatives

NASA Astrophysics Data System (ADS)

Sunil Kumar Reddy, N.; Badam, Rajashekar; Sattibabu, Romala; Molli, Muralikrishna; Sai Muthukumar, V.; Siva Sankara Sai, S.; Rao, G. Nageswara

2014-11-01

We report here the nonlinear optical (NLO) properties of eight bis-chalcones of D-π-A-π-D type. These dibenzylideneacetone (DBA) derivatives are synthesized by Claisen-Schmidt reaction. The compounds are characterized by UV-vis, FTIR, 1H NMR, 13C NMR, mass spectroscopy and powder XRD. By substituting different groups (electron withdrawing and electron donating) at 'para' and 'meta' positions of the aromatic ring, we observed an enhancement in second harmonic generation with substitution at 'para' position. These compounds have also showed higher two-photon absorption compared to other chalcones reported in literature. These compounds, exhibiting both second and third order NLO effects, are plausible candidate materials in photonic devices.

Withdrawal of ventilation at the patient's request in MND: a retrospective exploration of the ethical and legal issues that have arisen for doctors in the UK.

PubMed

Phelps, Kay; Regen, Emma; Oliver, David; McDermott, Chris; Faull, Christina

2017-06-01

Ventilatory support has benefits including prolonging survival for respiratory failure in motor neurone disease (MND). At some point some patients may wish to stop the intervention. The National Institute of Health and Care Excellence (NICE) guidance recommends research is needed on ventilation withdrawal. There is little literature focusing on the issues doctors encounter when withdrawing ventilation at the request of a patient. To identify and explore with doctors the ethical and legal issues that they had encountered in the withdrawal of ventilation at the request of a patient with MND. A retrospective thematic analysis of interviews of 24 doctors (including palliative care, respiratory, neurology and general practice) regarding their experiences with withdrawal of ventilation support from patients with MND. Respondents found withdrawal of ventilation at the request of patients with MND to pose legal, ethical and moral challenges in five themes: ethical and legal rights to withdrawal from treatment; discussions with family; discussions with colleagues; experiences of legal advice; issues contributing to ethical complexity. Though clear about the legality of withdrawal of treatment in theory, the practice led to ethical and moral uncertainty and mixed feelings. Many respondents had experienced negative reactions from other healthcare professionals when these colleagues were unclear of the distinction between palliation of symptoms, withdrawal of treatment and assisted death. Legal, ethical and practical guidance is needed for professionals who support a patient with MND who wishes to withdraw from ventilation. Open discussion of the ethical challenges is needed as well as education and support for professionals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A contingent payment model of smoking cessation: effects on abstinence and withdrawal.

PubMed

Heil, Sarah H; Tidey, Jennifer W; Holmes, Heather W; Badger, Gary J; Higgins, Stephen T

2003-04-01

The present study was designed to characterize nicotine withdrawal during a 5-day period in which smokers who were not trying to quit were offered monetary incentives to abstain while residing in their usual environments. Participants were randomly assigned to one of three groups. In two groups, monetary payment was delivered contingent on breath carbon monoxide levels (CO< or =8 ppm) indicating recent smoking abstinence, with the amount of payment differing between the two groups. The third group was a control group in which payment was delivered independent of smoking status. Participants provided CO samples three times per day (morning, afternoon- and evening) for 5 days (Monday-Friday). At each evening visit, all participants completed a nicotine withdrawal questionnaire and other questionnaires. Contingent payment significantly decreased expired-air CO and salivary cotinine levels as compared with the control group. No significant differences in abstinence were noted as a function of the amount paid. Participants in both contingent payment groups reported significantly more withdrawal symptoms than those in the noncontingent control group, including increases in anxiety and nervousness, impatience and restlessness, hunger, and desire to smoke. Such contingent payment procedures may provide an effective method for studying nicotine withdrawal in smokers that does not require the costly and inconvenient practice of housing research participants on a closed ward to prevent smoking.

Methyl group transfer upon gas phase decomposition of protonated methyl benzoate and similar compounds.

PubMed

Frański, Rafał; Gierczyk, Błażej; Zalas, Maciej; Jankowski, Wojciech; Hoffmann, Marcin

2018-05-01

Gas phase decompositions of protonated methyl benzoate and its conjugates have been studied by using electrospray ionization-collision induced dissociation-tandem mass spectrometry. Loss of CO 2 molecule, thus transfer of methyl group, has been observed. In order to better understand this process, the theoretical calculations have been performed. For methyl benzoate conjugates, it has been found that position of substituent affects the loss of CO 2 molecule, not the electron donor/withdrawing properties of the substituent. Therefore, electrospray ionization-mass spectrometry in positive ion mode may be useful for differentiation of isomers of methyl benzoate conjugates. Copyright © 2018 John Wiley & Sons, Ltd.

The comparative efficacy of first- versus second-generation electronic cigarettes in reducing symptoms of nicotine withdrawal.

PubMed

Lechner, William V; Meier, Ellen; Wiener, Josh L; Grant, DeMond M; Gilmore, Jenna; Judah, Matt R; Mills, Adam C; Wagener, Theodore L

2015-05-01

Currently, electronic cigarettes (e-cigarettes) are studied as though they are a homogeneous category. However, there are several noteworthy differences in the products that fall under this name, including potential differences in the efficacy of these products as smoking cessation aids. The current study examined the comparative efficacy of first- and second-generation e-cigarettes in reducing nicotine withdrawal symptoms in a sample of current smokers with little or no experience of using e-cigarettes. Twenty-two mildly to moderately nicotine-dependent individuals were randomized to a cross-over design in which they used first- and second-generation e-cigarettes on separate days with assessment of withdrawal symptoms directly prior to and after product use. A community-based sample recruited in the Midwest region of the United States reported a mean age of 28.6 [standard deviation (SD) = 12.9]. The majority were male (56.5%), Caucasian (91.3%), reported smoking an average of 15.2 (SD = 9.6) tobacco cigarettes per day, and a mean baseline carbon monoxide (CO) level of 18.7 parts per million (p.p.m.). Symptoms of withdrawal from nicotine were measured via the Mood and Physical Symptoms Scale. Analysis of changes in withdrawal symptoms revealed a significant time × product interaction F(1, 21)  = 5.057, P = 0.036, n(2) P  = 0.202. Participants experienced a larger reduction in symptoms of nicotine withdrawal after using second-generation compared with first-generation e-cigarettes. Second-generation e-cigarettes seem to be more effective in reducing symptoms of nicotine withdrawal than do first-generation e-cigarettes. © 2015 Society for the Study of Addiction.

The excretion and environmental effects of amoxicillin, ciprofloxacin, and doxycycline residues in layer chicken manure.

PubMed

Peng, Ping-cai; Wang, Yan; Liu, Long-yong; Zou, Yong-de; Liao, Xin-di; Liang, Juan-boo; Wu, Yin-bao

2016-05-01

The excretion rates and ecological risk to the environment of three commonly used veterinary antibiotics (VAs), amoxicillin, ciprofloxacin, and doxycycline, in layer hen manure during the application and withdrawal periods were investigated in a study consisting of a control group fed with VA-free basal diet and nine treatment groups consisted of three levels (200 mg/kg, 100 mg/kg, and 50 mg/kg) of amoxicillin (AMX), ciprofloxacin (CIP), or doxycycline (DOC). Each treatment group was replicated seven times with three layer hens per replication. Results of the study showed that the average excretion rates of AMX in the 200, 100, and 50 mg/kg groups were 67.88, 55.82, and 66.15%, respectively, while those for CIP and DOC were 47.84, 51.85, and 44.87% and 82.67, 94.39, and 95.72%, respectively. The concentrations of the above veterinary drugs in manure decreased sharply in the withdrawal period (7, 28, and 10 d, respectively), for AMX, DOC, and CIP. Neither AMX nor DOC was detected in the manure after the withdrawal period. In contrast to AMX and DOC, the excretion rate of CIP was significantly lower and thus had a longer residence time. Ecological risk study, estimated using hazard quotient values, showed that AMX in the 100 and 50 mg/kg groups posed no risk to the environment after d 1 of withdrawal, while CIP in the 50 mg/kg group posed no risk to the environment from d 5 of withdrawal. CIP in the 200 and 100 mg/kg groups required 10 d withdrawal in order to pose no risk to the environment. In contrast, DOC residue during withdrawal in the manure posed no risk to the environment, thus making it more environmentally safe. © 2016 Poultry Science Association Inc.

Synthesis and electronic factors in thermal cyclodimerization of functionalized aromatic trifluorovinyl ethers.

PubMed

Spraul, Bryan K; Suresh, S; Jin, Jianyong; Smith, Dennis W

2006-05-31

A series of 19 p-substituted aromatic trifluorovinyl ether compounds were prepared from versatile intermediate p-Br-C(6)H(4)-O-CF=CF(2) and underwent thermal radical mediated cyclodimerization to new difunctional compounds containing the 1,2-disubstituted perfluorocyclobutyl (PFCB) linkage. The synthetic scope demonstrates the functional group transformation tolerance of the fluorovinyl ether, and the dimers are useful as monomers for traditional step-growth polymerization methods. (19)F NMR spectra confirmed that p-substitution affects the trifluorovinyl ether group chemical shifts. The first kinetic studies and substituent effects on thermal cyclodimerization were performed, and the results indicated that electron-withdrawing groups slow the rate of cyclodimerization. The data were further analyzed using the Hammett equation, and reaction constants (rho) of -0.46 at 120 degrees C and -0.59 at 130 degrees C were calculated. This study presents the first liner free energy relationship reported for the cyclodimerization of aromatic trifluorovinyl ethers to PFCB compounds.

Cultivating Fluorescent Flowers with Highly Luminescent Carbon Dots Fabricated by a Double Passivation Method

PubMed Central

Chang, Tao; Zhao, Haiping; Du, Huanhuan; Liu, Shan; Wu, Baoshuang; Qin, Shenjun

2017-01-01

In this work, we present the fabrication of highly luminescent carbon dots (CDs) by a double passivation method with the assistance of Ca(OH)2. In the reaction process, Ca2+ protects the active functional groups from overconsumption during dehydration and carbonization, and the electron-withdrawing groups on the CD surface are converted to electron-donating groups by the hydroxyl ions. As a result, the fluorescence quantum yield of the CDs was found to increase with increasing Ca(OH)2 content in the reaction process. A blue-shift optical spectrum of the CDs was also found with increasing Ca(OH)2 content, which could be attributed to the increasing of the energy gaps for the CDs. The highly photoluminescent CDs obtained (quantum yield: 86%) were used to cultivate fluorescent carnations by a water culture method, while the results of fluorescence microscopy analysis indicated that the CDs had entered the plant tissue structure. PMID:28686178

Acetonitrile Ion Suppression in Atmospheric Pressure Ionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Colizza, Kevin; Mahoney, Keira E.; Yevdokimov, Alexander V.; Smith, James L.; Oxley, Jimmie C.

2016-11-01

Efforts to analyze trace levels of cyclic peroxides by liquid chromatography/mass spectrometry gave evidence that acetonitrile suppressed ion formation. Further investigations extended this discovery to ketones, linear peroxides, esters, and possibly many other types of compounds, including triazole and menadione. Direct ionization suppression caused by acetonitrile was observed for multiple adduct types in both electrospray ionization and atmospheric pressure chemical ionization. The addition of only 2% acetonitrile significantly decreased the sensitivity of analyte response. Efforts to identify the mechanism were made using various nitriles. The ion suppression was reduced by substitution of an acetonitrile hydrogen with an electron-withdrawing group, but was exacerbated by electron-donating or steric groups adjacent to the nitrile. Although current theory does not explain this phenomenon, we propose that polar interactions between the various functionalities and the nitrile may be forming neutral aggregates that manifest as ionization suppression.

The investigation of substituent effects on the fragmentation pathways of pentacoordinated phenoxyspirophosphoranes by ESI-MSn.

PubMed

Cui, Xiaoyan; Sun, Can; Zhao, Pei; Wang, Yanyan; Guo, Yanchun; Zhao, Yufen; Cao, Shuxia

2018-04-01

The fragmentation pathways of pentacoordinated phenoxyspirophosphoranes were investigated in the positive mode by electrospray ionization multistage mass spectrometry. The results demonstrate that the sodium adducts of the title compounds undergo two competitive fragmentation pathways, and the fragmentation patterns are heavily dependent on the various substituent patterns at the phenolic group. An electron-withdrawing substituent at the ortho-position always results in the removal of a corresponding phenol analogue, while cleavage by spiroring opening becomes the predominant fragmentation pathway if an electron-donating substituent is at the phenolic group. The substituent effects on the competitive fragmentation pathways were further elucidated by theoretical calculations, single crystal structure analysis, and high-resolution mass spectrometry. The results contribute to the understanding of the gas-phase fragmentation reactions and the structure identification of spirophosphorane analogues by electrospray ionization multistage mass spectrometry. Copyright © 2018 John Wiley & Sons, Ltd.

Gabapentin-base synthesis and theoretical studies of biologically active compounds: N-cyclohexyl-3-oxo-2-(3-oxo-2-azaspiro[4.5] decan-2-yl)-3-arylpropanamides and N-(tert-butyl)-2-(3-oxo-2-azaspiro[4.5]decan-2-yl)-2-arylacetamide derivatives

NASA Astrophysics Data System (ADS)

Amirani Poor, Mahboobe; Darehkordi, Ali; Anary-Abbasinejad, Mohammad; Mohammadi, Marziyeh

2018-01-01

An intermolecular Ugi reaction of 2-(1-(aminomethyl)cyclohexyl)acetic acid (gabapentin) with glyoxal and cyclohexyl isocyanide or aromatic aldehyde and tertbutyl isocyanide under mild conditions in ethanol have been developed to produce two novel class of N-cyclohexyl-3-(aryl)-3-oxo-2-(3-oxo-2-azaspiro[4.5]decan-2-yl)propanamideins and N-(tert-butyl)-2-(3-oxo-2-azaspiro[4.5]decan-2-yl)-2-arylacetamide derivatives in good to excellent yields. This presents the first report for the intermolecular Ugi three component reaction of gabapentin, glyoxal, and an isocyanide. Also according to the theoretical studies the electron-donating groups increase the strength of intramolecular hydrogen bond and electron-withdrawing groups decrease the strength of intramolecular hydrogen bond.

Impact of hot temperature on end-face geometry of LC/UPC connectors

NASA Astrophysics Data System (ADS)

Thongdaeng, Rutsuda; Worasucheepb, Duangrudee; Wangsan, Sathit; Chaichok, Wansan

2014-09-01

The fiber withdrawal of Group 4 (mated-thermal cycle) was observed up to 100 nm as in previous work1. We predict that this withdrawal is mainly caused by the impact of hot temperature (at 75ºC) based on GR-3262 thermal cycle test profile repeated 21 cycles over 7 days; and thus, it was studies here for the purpose of reducing test time. All connectors were separated into four groups: 1) unmated-stored at room temperature, 2) mated-stored at room temperature, 3) unmated-stored at hot temperature, and 4) mated-stored at hot temperature. The hot temperature test was performed on Groups 3 and 4 for 1 hour, while Groups 1 and 2 was left at room temperature. The sample size of each group is 28 LC/UPC connectors. Radius of curvature, fiber height and apex offset were measured before and after that 1 hour. The fiber withdrawal up to 100 nm is found in Group 4 (mated-hot temperature), but no changes are observed in Groups 1-3. These results confirm the impact of hot temperature on fiber height, same as the thermal cycle test in previous work1. Afterward, Group 1-4 were unmated at room temperature for 1 day, 1 week, and 1 month. No significant change in fiber height is found. On the contrary, when Group 1-4 were re-tested as being mated at hot temperature for 1 hour, the fiber withdrawal up to 100 nm is now found in Group 1-3. However, the additional withdrawal up to 50 nm is still observed in Group 4.

Impact of Different e-Cigarette Generation and Models on Cognitive Performances, Craving and Gesture: A Randomized Cross-Over Trial (CogEcig).

PubMed

Caponnetto, Pasquale; Maglia, Marilena; Cannella, Maria Concetta; Inguscio, Lucio; Buonocore, Mariachiara; Scoglio, Claudio; Polosa, Riccardo; Vinci, Valeria

2017-01-01

Introduction: Most electronic-cigarettes (e-cigarette) are designed to look like traditional cigarettes and simulate the visual, sensory, and behavioral aspects of smoking traditional cigarettes. This research aimed to explore whether different e-cigarette models and smokers' usual classic cigarettes can impact on cognitive performances, craving and gesture. Methods: The study is randomized cross-over trial designed to compare cognitive performances, craving, and gesture in subjects who used first generation electronic cigarettes, second generation electronic cigarettes with their usual cigarettes. (Trial registration: ClinicalTrials.gov number NCT01735487). Results: Cognitive performance was not affected by "group condition." Within-group repeated measures analyses showed a significant time effect, indicating an increase of participants' current craving measure in group "usual classic cigarettes (group C)," "disposable cigalike electronic cigarette loaded with cartridges with 24 mg nicotine (group H), second generation electronic cigarette, personal vaporizer model Ego C, loaded with liquid nicotine 24 mg (group E). Measures of gesture not differ over the course of the experiment for all the products under investigation Conclusion: All cognitive measures attention, executive function and working memory are not influenced by the different e-cigarette and gender showing that in general electronics cigarettes could become a strong support also from a cognitive point of view for those who decide to quit smoking. It seems that not only craving and other smoke withdrawal symptoms but also cognitive performance is not only linked to the presence of nicotine; this suggests that the reasons behind the dependence and the related difficulty to quit smoking needs to be looked into also other factors like the gesture. www.ClinicalTrials.gov, identifier NCT01735487.

Impact of Different e-Cigarette Generation and Models on Cognitive Performances, Craving and Gesture: A Randomized Cross-Over Trial (CogEcig)

PubMed Central

Caponnetto, Pasquale; Maglia, Marilena; Cannella, Maria Concetta; Inguscio, Lucio; Buonocore, Mariachiara; Scoglio, Claudio; Polosa, Riccardo; Vinci, Valeria

2017-01-01

Introduction: Most electronic-cigarettes (e-cigarette) are designed to look like traditional cigarettes and simulate the visual, sensory, and behavioral aspects of smoking traditional cigarettes. This research aimed to explore whether different e-cigarette models and smokers' usual classic cigarettes can impact on cognitive performances, craving and gesture. Methods: The study is randomized cross-over trial designed to compare cognitive performances, craving, and gesture in subjects who used first generation electronic cigarettes, second generation electronic cigarettes with their usual cigarettes. (Trial registration: ClinicalTrials.gov number NCT01735487). Results: Cognitive performance was not affected by “group condition.” Within-group repeated measures analyses showed a significant time effect, indicating an increase of participants' current craving measure in group “usual classic cigarettes (group C),” “disposable cigalike electronic cigarette loaded with cartridges with 24 mg nicotine (group H), second generation electronic cigarette, personal vaporizer model Ego C, loaded with liquid nicotine 24 mg (group E). Measures of gesture not differ over the course of the experiment for all the products under investigation Conclusion: All cognitive measures attention, executive function and working memory are not influenced by the different e-cigarette and gender showing that in general electronics cigarettes could become a strong support also from a cognitive point of view for those who decide to quit smoking. It seems that not only craving and other smoke withdrawal symptoms but also cognitive performance is not only linked to the presence of nicotine; this suggests that the reasons behind the dependence and the related difficulty to quit smoking needs to be looked into also other factors like the gesture. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01735487. PMID:28337155

The Hammett relationship and reactions in the excited electronic state: hemithioindigo Z/E-photoisomerization.

PubMed

Cordes, Thorben; Schadendorf, Torsten; Priewisch, Beate; Rück-Braun, Karola; Zinth, Wolfgang

2008-01-31

The photochemical reaction dynamics of a set of photochromic compounds based on thioindigo and stilbene molecular parts (hemithioindigos, HTI) are presented. Photochemical Z/E isomerization around the central double bond occurs with time constants of 216 ps (Z --> E) and 10 ps (E --> Z) for a 5-methyl-hemithioindigo. Chemical substitution on the stilbene moiety causes unusually strong changes in the reaction rate. Electron-donating substituents in the position para to the central double bond (e.g., para-methoxy) strongly accelerate the reaction, while the reaction is drastically slowed by electron-withdrawing groups in this position (e.g., para-nitrile). We correlate the experimental data of seven HTI-compounds in a quantitative manner using the Hammett equation and present a qualitative explanation for the application of ground-state Hammett constants to describe the photoisomerization reaction.

A new look into conformational, vibrational and electronic structure analysis of 3,4-dimethoxybenzonitrile.

PubMed

Arjunan, V; Devi, L; Remya, P; Mohan, S

2013-09-01

The FTIR and FT-Raman spectra of 3,4-dimethoxybenzonitrile (34DMBN) have been analysed. Quantum chemical studies were performed with B3LYP method using 6-311++G(d,p), 6-31G(d,p) and cc-pVTZ basis sets. The electron donating effect of -OCH3 and electron withdrawing effect of -C≡N groups on the ring parameters were thoroughly analysed. The structural parameters, energies, thermodynamic properties, vibrational frequencies and the NBO charges of 34DMBN were determined. The (1)H and (13)C chemical shifts with respect to TMS were investigated and also calculated theoretically using the gauge independent atomic orbital method and compared with the experimental data. The delocalisation energy of different types of bonding interactions was investigated. Copyright © 2013 Elsevier B.V. All rights reserved.

Solution-Processable Balanced Ambipolar Field-Effect Transistors Based on Carbonyl-Regulated Copolymers.

PubMed

Yang, Chengdong; Fang, Renren; Yang, Xiongfa; Chen, Ru; Gao, Jianhua; Fan, Hanghong; Li, Hongxiang; Hu, Wenping

2018-04-04

It is very important to develop ambipolar field effect transistors to construct complementary circuits. To obtain balanced hole- and electron-transport properties, one of the key issues is to regulate the energy levels of the frontier orbitals of the semiconductor materials by structural tailoring, so that they match well with the electrode Fermi levels. Five conjugated copolymers were synthesized and exhibited low LUMO energy levels and narrow bandgaps on account of the strong electron-withdrawing effect of the carbonyl groups. Polymer thin film transistors were prepared by using a solution method and exhibited high and balanced hole and electron mobility of up to 0.46 cm 2  V -1  s -1 , which suggested that these copolymers are promising ambipolar semiconductor materials. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hyperpolarizable compounds and devices fabricated therefrom

DOEpatents

Therien, Michael J.; DiMagno, Stephen G.

1998-01-01

Substituted compounds having relatively large molecular first order hyperpolarizabilities are provided, along with devices and materials containing them. In general, the compounds bear electron-donating and electron-withdrawing chemical substituents on a polyheterocyclic core.

Abrupt opium discontinuation has no significant triggering effect on acute myocardial infarction.

PubMed

Masoomi, Mohammad; Zare, Jahangir; Nasri, Hamidreza; Mirzazadeh, Ali; Sheikhvatan, Mehrdad

2011-04-01

A deleterious effect of withdrawal symptoms due to abrupt discontinuation of opium on the cardiovascular system is one of the recent interesting topics in the cardiovascular field. The current study hypothesized that the withdrawal syndrome due to discontinuing opium might be an important trigger for the appearance of acute myocardial infarction. Eighty-one opium-addicted individuals who were candidates for cardiovascular clinical evaluation and consecutively hospitalized in the coronary care unit (CCU) ward of Shafa Hospital in Kerman between January and July 2009 were included in the study and categorized in the case group, including patients experiencing withdrawal symptoms within 6-12 h after the reduced or discontinued use of opium according to the Diagnostic and Statistical Manual of Mental Disorders-revised IV version (DSM-IV-R) criteria for opium dependence and withdrawal, and the control group, without opium withdrawal symptoms. The appearance of acute myocardial infarction was compared between the two groups using multivariable regression models. Acute myocardial infarction occurred in 50.0% of those with withdrawal symptoms and in 45.1% of patients without evidence of opium withdrawal (P = 0.669). Multivariable analysis showed that opium withdrawal symptoms were not a trigger for acute myocardial infarction adjusting for demographic characteristics, marital status, education level and common coronary artery disease risk profiles [odds ratio (OR) = 0.920, 95% confidence interval (CI) = 0.350-2.419, P = 0.866]. Also, daily dose of opium before reducing or discontinuing use did not predict the appearance of myocardial infarction in the presence of confounder variables (OR = 0.975, 95% CI = 0.832-1.143, P = 0.755). Withdrawal syndrome due to abrupt discontinuation of opium does not have a triggering role for appearance of acute myocardial infarction.

Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure.

PubMed

Casey, Michael J; Wen, Xuerong; Kayler, Liise K; Aiyer, Ravi; Scornik, Juan C; Meier-Kriesche, Herwig-Ulf

2014-08-15

When kidney transplants fail, transplant medications are discontinued to reduce immunosuppression-related risks. However, retransplant candidates are at risk for allosensitization which prolonging immunosuppression may minimize. We hypothesized that for these patients, a prolonged immunosuppression withdrawal after graft failure preserves nonsensitization status (PRA 0%) better than early immunosuppression withdrawal. We retrospectively examined subjects transplanted at a single center between July 1, 1999 and December 1, 2009 with a non-death-related graft loss. Subjects were stratified by timing of immunosuppression withdrawal after graft loss: early (≤3 months) or prolonged (>3 months). Retransplant candidates were eligible for the main study where the primary outcome was nonsensitization at retransplant evaluation. Non-retransplant candidates were included in the safety analysis only. We found 102 subjects with non-death-related graft loss of which 49 were eligible for the main study. Nonsensitization rates at retransplant evaluation were 30% and 66% for the early and prolonged immunosuppression withdrawal groups, respectively (P=0.01). After adjusting for cofactors such as blood transfusion and allograft nephrectomy, prolonged immunosuppression withdrawal remained significantly associated with nonsensitization (adjusted odds ratio=5.78, 95% CI [1.37-24.44]). No adverse safety signals were seen in the prolonged immunosuppression withdrawal group compared to the early immunosuppression withdrawal group. These results suggest that prolonged immunosuppression may be a safe strategy to minimize sensitization in retransplant candidates and provide the basis for larger or prospective studies for further verification.

Acute and chronic glue sniffing effects and consequences of withdrawal on aggressive behavior.

PubMed

Bouchatta, Otmane; Ouhaz, Zakaria; Ba-Mhamed, Saadia; Kerekes, Nóra; Bennis, Mohamed

2016-05-01

Drug abuse act on brain mechanisms that cause a high-risk individual to engage in aggressive and violent behavior. While a drug-violence relationship exists, the nature of this relationship is often complex, with intoxication, neurotoxic, and withdrawal effects often being confused and/or confounded. Glue sniffing is often a springboard to the abuse of more addictive drugs. Despite its high prevalence and serious consequences, we know relatively little about the aggressive behavioral effects of volatile inhalants abuse, especially glue. The aim of the present study was to investigate the link between the duration of glue exposure, a common substance abuse problem in Morocco, and the level of aggressive behavior during withdrawal. For this we used the isolation-induced aggression model "residents" in three groups of mice. The first group served as control resident animals (n=10, without exposure); the second group as experimental resident mice (n=10) tested before and after acute (first day) and chronic exposure to the glue, and at 1 and 2weeks of withdrawal; and the third group of 10 intruder animals. The results showed that the number of attacks decreased (halved) and the latency of the first attack increased (doubled) following acute glue sniffing. However, the effects of chronic exposure and of 1week of withdrawal led to an increase in the intensity of agonistic encounters. After 2weeks of withdrawal, the intensity of aggressive behavior decreased again. These results indicated that chronic glue exposure and the first week of withdrawal are associated with increased aggression in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

[Comparative study on effects between electroacupuncture and auricular acupuncture for methamphetamine withdrawal syndrome].

PubMed

Liang, Yan; Xu, Bo; Zhang, Xue-Chun; Zong, Lei; Chen, Yue-Lai

2014-03-01

To observe the efficacy difference of electroacupuncture and auricular acupuncture in the treatment of methamphetamine withdrawal syndrome. Ninety male patients of methamphetamine addiction were randomized into an electroacupuncture group, an auricular acupuncture group and a control group, 30 cases in each one. In the electroacupuncture group, Neiguan (PC 6), Shenmen (HT 7), Zusanli (ST 36), Sanyinjiao (SP 6), Jiaji (EX-B 2) at T5 and L2 were selected bilaterally. In the auricular acupuncture group, jiaogan (AH(6a)), shenmen (TF4), fei (CO14) and gan (CO12) were selected unilaterally. The treatment was given 3 times a week, totally 12 treatments were required. In the control group, no any intervention was applied. Separately, before treatment and after 1, 2, 3 and 4 weeks treatment, the scores of methamphetamine withdrawal syndrome, Hamilton anxiety scale and Hamilton depression scale were observed in each group. The total score of methamphetamine withdrawal syndrome, anxiety score and depression score were obviously reduced in 2, 3 and 4 weeks of treatment as compared with those before treatment in the electroacupuncture group and the auricular acupuncture group (all P < 0.05), and showed a trend of gradual decline as the extension of treatment. In 1,2,3,4 weeks of treatment, the total score of withdrawal syndrome, anxiety score and depression score in the electroacupuncture group and auricular acupuncture group were lower significantly than those in the control group (all P < 0.05), in which, the total score of withdrawal syndrome in the electroacupuncture group was lower significantly than that in the auricular acupuncture group in the 4th week of treatment (3.69 +/- 2.446 vs 5.73 +/- 3.169, P < 0.05); the anxiety scores were lower significantly than those in the auricular acupuncture group in 3 and 4 weeks of treatment (8.19 +/- 4.57 vs 9.65 +/- 4.24, 5.27 +/- 2.89 vs 7.38 +/- 3.10, both P < 0.05); the depression scores were lower significantly than those in the auricular acupuncture group in 2, 3 and 4 weeks of treatment (15.35 +/- 5.64 vs 19.81 +/- 5.37, 10.96 +/- 4.52 vs 15.00 +/- 4.53, 7.96 +/- 2.69 vs 12.35 +/- 3.59, all P < 0.05). Electroacupuncture at the body points and auricular acupuncture play the therapeutic role in the treatment of methamphetamine withdrawal syndrome, anxiety and depression. The longer time the treatment is with electroacupuncture at the body points, the more obvious the efficacy will be on the above symptoms.

Efficient n-doping of graphene films by APPE (aminophenyl propargyl ether): a substituent effect.

PubMed

Kim, Youngsoo; Yoo, Je Min; Jeon, Hak Rim; Hong, Byung Hee

2013-11-14

We report the synthesis and applications of APPE (aminophenyl propargyl ether) as a novel n-type dopant for graphene. The characteristics of APPE-doped graphene films were investigated using Raman spectroscopy as well as electron transport measurements. The Raman 2D/G peak ratio decreased by more than 40%, and the minimum conductivity voltage (Dirac voltage) was shifted to -133 V as the pristine graphene was doped with APPE, indicating that the graphene was strongly n-doped. We suppose that the electron donating property of the amine group (-NH2) is the origin of such an intense n-doping effect. In contrast, a similar molecule with an electron withdrawing nitro group (-NO2) (nitrophenyl propargyl ether, NPPE) showed a slight p-doping effect. Thus, we conclude that the doping effect of a molecular framework strongly depends on the functional substituents, which can be represented by the Hammett equation. We also confirmed that the sheet resistance of the APPE doped graphene film was reduced by ∼70%, which is crucial to enhance the electrical conductivity of graphene for various electronic applications. In addition, the acetylene group of APPE appears promising to be utilized in "click chemistry" to further functionalize the π-surface of graphene for sensors and bio applications.

Pretreatment with remifentanil, fentanyl, or lidocaine to prevent withdrawal after rocuronium using venous occlusion technique in children and adolescents: a prospective randomized placebo-controlled double-blind study.

PubMed

Abu-Halaweh, S A; Aloweidi, A K; Qudaisat, I Y; Al-Hussami, M O; Al Zaben, K R; Abu-Halaweh, A S

2014-12-01

Pain caused by intravenous injection of the muscle relaxant rocuronium bromide is common in children and adolescents. The cause of this unwanted effect is still unclear, and different pretreatment drugs have been administered in attempts to alleviate this side effect, with varying degrees of success. This study used a 60-s venous occlusion technique to evaluate the effectiveness of pretreatment with lidocaine, fentanyl, or remifentanil in preventing pain-induced withdrawal caused by intravenous injection of rocuronium bromide during the induction of general anesthesia. One hundred and one child and adolescent patients, ASA Ι-II, requiring various surgical procedures under general anesthesia with muscle relaxation and mechanical ventilation, were enrolled. Patients were allocated randomly using computer-generated randomization into one of four pretreatment groups: a remifentanil group (1 µg/kg, n = 25), fentanyl group (1 µg/kg, n = 26), lidocaine 1% group (0.5 mg/kg, n = 25), and normal saline group (n = 25). Drug doses were prepared in normal saline to a total volume of 5 ml. Venous occlusion was applied 10 cm above the venous access site. Pretreatment drugs were injected and retained for 60 s at the site of injection by an anesthetist blinded to group allocation. After release of the tourniquet, rocuronium (0.5 mg/kg) was then injected over 5 s, and withdrawal was recorded by another anesthetist blinded to group allocation. Descriptive statistics, analysis of variance, and a chi-squared test were used to statistically analyze the results as appropriate. Compared to normal saline, all other pretreatment groups scored a significantly lower mean of withdrawal response (P < 0.001). Lidocaine was superior to both remifentanil (P < 0.05) and fentanyl (P < 0.05) in suppressing the withdrawal response to rocuronium injection. Remifentanil was superior to fentanyl in suppressing the withdrawal response caused by rocuronium injection (P < 0.001). Using a venous occlusion technique for 60 s, lidocaine was found to be most effective in preventing the withdrawal effect caused by rocuronium injection in children and adolescents. Lidocaine was superior to remifentanil which, in turn, was more effective than fentanyl.

Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects

PubMed Central

2013-01-01

Background Alzheimer’s disease (AD) as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh) concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE) inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease. Results Design, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC50 = 0.91 ± 0.045 μM) compared to donepezil (IC50 = 0.14 ± 0.03 μM). The results of the enzyme inhibition test (Ellman test) showed that electron withdrawing groups like Cl, F and NO2 can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta) afforded a favorable potency (IC50 = 5.5 ± 0.7 μM). Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a. Conclusions Synthesized compounds 4a-4l could be proposed as potential anticholinesterase agents. PMID:23758724

Effect of Sirtuin-1 on Synaptic Plasticity in Nucleus Accumbens in a Rat Model of Heroin Addiction.

PubMed

Xia, Baijuan; Li, Yixin; Li, Rongrong; Yin, Dan; Chen, Xingqiang; Li, Jie; Liang, Wenmei

2018-06-05

BACKGROUND Synaptic plasticity plays an important role in the process of addiction. This study investigated the relationship between synaptic plasticity and changes in addictive behavior and examined the expression of synaptic plasticity-associated proteins and genes in the nucleus accumbens (NAc) region in different rat models. MATERIAL AND METHODS Heroin addiction, SIRT1-overexpression, and SIRT1-silenced rat models were established. Polymerase chain reaction gene chip technology, immunohistochemistry, Western blotting, and transmission electron microscopy were used to detect changes in synaptic plasticity-related gene and protein expression, and changes in the ultrastructure of synapses, in the NAc. RESULTS Naloxone withdrawal symptoms appeared in the SIRT1-overexpression group. In the SIRT1-silenced group the symptoms were reduced. Immunohistochemistry and Western blotting results showed that FOXO1 expression decreased in the heroin addiction (HA) group but increased in the SIRT1-silenced group (p<0.05). The expression of Cdk5, Nf-κB, PSD95, and Syn was enhanced in the HA group (p<0.05) and further increased in the SIRT1-overexpression group but were reduced in the SIRT1-silenced group (p<0.05). The number of synapses increased in the HA group (p<0.05) along with mitochondrial swelling in the presynaptic membrane and obscuring of the synaptic cleft. CONCLUSIONS SIRT1 and other synaptic plasticity-related genes in NAc are involved in the regulation of heroin addiction. SIRT1 overexpression can increase behavioral sensitization in the NAc of rats, and SIRT1 silencing might ease withdrawal symptoms and reduce conditioned place preferences.

Estimated Ground-Water Withdrawals from the Death Valley Regional Flow System, Nevada and California, 1913-98

USGS Publications Warehouse

Moreo, Michael T.; Halford, Keith J.; La Camera, Richard J.; Laczniak, Randell J.

2003-01-01

Ground-water withdrawals from 1913 through 1998 from the Death Valley regional flow system have been compiled to support a regional, three-dimensional, transient ground-water flow model. Withdrawal locations and depths of production intervals were estimated and associated errors were reported for 9,300 wells. Withdrawals were grouped into three categories: mining, public-supply, and commercial water use; domestic water use; and irrigation water use. In this report, groupings were based on the method used to estimate pumpage. Cumulative ground-water withdrawals from 1913 through 1998 totaled 3 million acre-feet, most of which was used to irrigate alfalfa. Annual withdrawal for irrigation ranged from 80 to almost 100 percent of the total pumpage. About 75,000 acre-feet was withdrawn for irrigation in 1998. Annual irrigation withdrawals generally were estimated as the product of irrigated acreage and application rate. About 320 fields totaling 11,000 acres were identified in six hydrographic areas. Annual application rates for high water-use crops ranged from 5 feet in Penoyer Valley to 9 feet in Pahrump Valley. The uncertainty in the estimates of ground-water withdrawals was attributed primarily to the uncertainty of application rate estimates. Annual ground-water withdrawal was estimated at about 90,000 acre-feet in 1998 with an assigned uncertainty bounded by 60,000 to 130,000 acre-feet.

Hyperpolarizable compounds and devices fabricated therefrom

DOEpatents

Therien, M.J.; DiMagno, S.G.

1998-07-21

Substituted compounds having relatively large molecular first order hyperpolarizabilities are provided, along with devices and materials containing them. In general, the compounds bear electron-donating and electron-withdrawing chemical substituents on a polyheterocyclic core. 13 figs.

Biocatalytic degradation of pharmaceuticals, personal care products, industrial chemicals, steroid hormones and pesticides in a membrane distillation-enzymatic bioreactor.

PubMed

Asif, Muhammad B; Hai, Faisal I; Kang, Jinguo; van de Merwe, Jason P; Leusch, Frederic D L; Price, William E; Nghiem, Long D

2018-01-01

Laccase-catalyzed degradation of a broad spectrum of trace organic contaminants (TrOCs) by a membrane distillation (MD)-enzymatic membrane bioreactor (EMBR) was investigated. The MD component effectively retained TrOCs (94-99%) in the EMBR, facilitating their continuous biocatalytic degradation. Notably, the extent of TrOC degradation was strongly influenced by their molecular properties. A significant degradation (above 90%) of TrOCs containing strong electron donating functional groups (e.g., hydroxyl and amine groups) was achieved, while a moderate removal was observed for TrOCs containing electron withdrawing functional groups (e.g., amide and halogen groups). Separate addition of two redox-mediators, namely syringaldehyde and violuric acid, further improved TrOC degradation by laccase. However, a mixture of both showed a reduced performance for a few pharmaceuticals such as primidone, carbamazepine and ibuprofen. Mediator addition increased the toxicity of the media in the enzymatic bioreactor, but the membrane permeate (i.e., final effluent) was non-toxic, suggesting an added advantage of coupling MD with EMBR. Copyright © 2017 Elsevier Ltd. All rights reserved.

Control of exciton confinement in quantum dot-organic complexes through energetic alignment of interfacial orbitals.

PubMed

Frederick, Matthew T; Amin, Victor A; Swenson, Nathaniel K; Ho, Andrew Y; Weiss, Emily A

2013-01-09

This paper describes a method to control the quantum confinement, and therefore the energy, of excitonic holes in CdSe QDs through adsorption of the hole-delocalizing ligand phenyldithiocarbamate, PTC, and para substitutions of the phenyl ring of this ligand with electron-donating or -withdrawing groups. These substitutions control hole delocalization in the QDs through the energetic alignment of the highest occupied orbitals of PTC with the highest density-of-states region of the CdSe valence band, to which PTC couples selectively.

Regioselective Formation of (E)-β-Vinylstannanes with a Topologically Controlled Molybdenum-Based Alkyne Hydrostannation Catalyst.

PubMed

Mandla, Kyle A; Moore, Curtis E; Rheingold, Arnold L; Figueroa, Joshua S

2018-06-04

The regioselective formation of (E)-β-vinylstannanes has been a long-standing challenge in transition-metal-catalyzed alkyne hydrostannation. Herein, we report a well-defined molybdenum-based system featuring two encumbering m-terphenyl isocyanides that reliably and efficiently delivers (E)-β-vinylstannanes from a range of terminal and internal alkynes with high regioselectivity. The system is particularly effective for aryl alkynes and can discriminate between alkyl chains of low steric hindrance in unsymmetrically substituted dialkyl alkynes. Catalytic hydrostannation with this system is also characterized by an electronic effect that leads to a decrease in regioselectivity when electron-withdrawing groups are present on the alkyne substrate. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A new synthetic approach to functionalize pyrimido[4,5-b]quinoline-2,4(1H,3H)-diones via a three-component one-pot reaction.

PubMed

Aknin, Karen; Desbène-Finck, Stéphanie; Helissey, Philippe; Giorgi-Renault, Sylviane

2010-02-01

Functionalized pyrimido[4,5-b]quinoline-2,4 (1H,3H)-diones were synthesized by a three-component one-pot reaction involving barbituric acid, aldehydes, and anilines. The use of commercially available anilines allowed the facile syntheses of pyrimido[4,5-b]quinolinediones substituted in all the positions on the benzene ring with electron donor or electron withdrawing groups. This straightforward method circumvents the preparation of unstable substituted 2-aminobenzaldehydes that limits the scope of previously described syntheses. Furthermore, access to the 5-substituted derivatives is now also possible starting from aliphatic or aromatic aldehydes. Our strategy and methodology offer significant and practical improvements over other methodologies.

Comprehensive investigation of the excited-state dynamics of push-pull triphenylamine dyes as models for photonic applications.

PubMed

Ishow, Eléna; Clavier, Gilles; Miomandre, Fabien; Rebarz, Mateusz; Buntinx, Guy; Poizat, Olivier

2013-09-07

A series of emitting push-pull triarylamine derivatives, models of their widely used homologues in photonics and organic electronics, was investigated by steady-state and time-resolved spectroscopy. Their structural originality stems from the sole change of the electron-withdrawing substituent X (-H: 1, -CN: 2, -NO2: 3, -CHC(CN)2: 4), giving rise to efficient emission tuning from blue to red upon increasing the X electron-withdrawing character. All compounds are highly fluorescent in alkanes. The more polar compounds 2-4 undergo considerable Stokes shift and emission quenching in polar solvents. Femtosecond transient absorption data allowed us to identify the nature of the emissive state which varies as a function of the compound and surrounding polarity. A long-lived ππ* excited state with weak charge transfer character was found for 1. This excited state evolves into a long-lived ICT state with red-shifted emission for 2 in polar solvents. For 3 and 4, the ICT state is directly populated in all solvents. Long-lived and emissive in n-hexane, it relaxes in toluene to a new ICT' conformation with stronger charge transfer character and enhanced Stokes shift. In more polar THF, ethanol, and nitrile solvents, ICT relaxes to a dark excited state ICT'' with viscosity-dependent kinetics (<10 ps). The ICT'' state lifetime drops with increasing solvent polarity (150 ps for 3 in THF, 8.5 ps in butyronitrile, 1.9 ps in acetonitrile), denoting an efficient radiationless deactivation to the ground state (back charge transfer). This result reveals a very small S0-S1 energy gap at the relaxed ICT'' geometry, with a possible close-lying S0-S1 conical intersection, which suggests that the ICT → ICT'' process results from a structural change involving a large-amplitude molecular distortion. This fast structural change can account for the strong fluorescence quenching observed for 3 and 4 in polar solvents. Finally, the magnitude of intersystem crossing between the singlet and triplet excited states largely depends on the electron-deficient X unit and the solvent itself. These observations help one conclude on the prevailing role played by the electron-withdrawing groups and the surrounding polarity in the photophysical performances of triphenylamine derivatives, largely employed in numerous emissive solid-state devices.

Exercise deprivation increases negative mood in exercise-addicted subjects and modifies their biochemical markers.

PubMed

Antunes, Hanna Karen Moreira; Leite, Geovana Silva Fogaça; Lee, Kil Sun; Barreto, Amaury Tavares; Santos, Ronaldo Vagner Thomatieli Dos; Souza, Helton de Sá; Tufik, Sergio; de Mello, Marco Tulio

2016-03-15

The aim of this study was to identify the possible association between biochemical markers of exercise addiction and affective parameters in a sample of athletes during 2weeks of withdrawal exercise. Eighteen male runners were distributed into a control group (n=10) composed of runners without exercise addiction symptoms and an exercise addiction group (n=8) composed of runners with exercise addiction symptoms. The volunteers performed a baseline evaluation that included affective questionnaires, blood samples, body composition and an aerobic test performed at ventilatory threshold I. After the baseline evaluation, the groups started an exercise withdrawal period that was sustained for 2weeks. During exercise withdrawal, an actigraph accelerometer was used to monitor the movement index, and CK and LDH were measured in blood samples to validate the non-exercise practice. At the end of the exercise withdrawal period, a blood collection, aerobic test and mood scale was performed in the re-test. The results showed that at the end of the experimental protocol, when compared with the control group, the exercise addiction group showed an increase in depression, confusion, anger, fatigue and decreased vigor mood that improved post-exercise, along with low levels of anandamide at all time-points evaluated and a modest increase in β-endorphin post-exercise. Moreover, the exercise addiction group showed a decrease in oxygen consumption and respiratory exchange ratio after the exercise withdrawal period, which characterized a detraining phenomenon. Our data suggest that a 2-week withdrawal exercise period resulted in an increase of negative mood in exercise addiction; additionally, exercise addiction showed low levels of anandamide. Copyright © 2016 Elsevier Inc. All rights reserved.

A double-blind, placebo-controlled trial of dextromethorphan combined with clonidine in the treatment of heroin withdrawal.

PubMed

Lin, Shih-Ku; Pan, Chun-Hung; Chen, Chia-Hui

2014-08-01

Dextromethorphan has been reported to ameliorate opioid withdrawal symptoms in both animal and human subjects. In the present study, we investigated the efficacy of dextromethorphan as an add-on medication in heroin detoxification treatment in a double-blind, placebo-controlled design. Sixty-five heroin-dependent patients (male, 63; female, 2) participated in this inpatient detoxification trial after giving informed consent. Clonidine 0.075 mg 4 times a day was given as an antiwithdrawal medication at baseline. Each patient was then randomly assigned to treatment with either dextromethorphan 60 mg or placebo 4 times a day as additional medication. Flurazepam 30 mg was given before bedtime for insomnia. Other medications that were allowed included loperamide for diarrhea and lorazepam for agitation. Participants were monitored using the Objective Opioid Withdrawal Scale 3 times a day as the primary outcome to compare drug efficacy between groups. Generalized estimating equation model analysis revealed that the Objective Opioid Withdrawal Scale had no group difference between dextromethorphan and placebo group overall (P = 0.29), whereas a significant difference between groups was found during day 3 to day 6 (P = 0.04) by post hoc analysis. There was no difference in the Clinical Global Impression Scale, patient's impression of treatment, and use of ancillary medications between groups. No severe adverse effects were noticed. We suggest that dextromethorphan has some beneficial effect in attenuating the severity of opioid withdrawal symptoms and can be used as an adjunction medication in the treatment of opioid withdrawal, whereas the exact efficacy needs further investigation.

Standardized Passiflora incarnata L. Extract Reverts the Analgesia Induced by Alcohol Withdrawal in Rats.

PubMed

Schunck, Rebeca Vargas Antunes; Macedo, Isabel Cristina; Laste, Gabriela; de Souza, Andressa; Valle, Marina Tuerlinckx Costa; Salomón, Janaína L O; Nunes, Ellen Almeida; Campos, Andreia Cristina Wildner; Gnoatto, Simone Cristina Baggio; Bergold, Ana Maria; Konrath, Eduardo L; Dallegrave, Eliane; Arbo, Marcelo Dutra; Torres, Iraci L S; Leal, Mirna Bainy

2017-08-01

Passiflora incarnata L. (Passifloraceae) has been traditionally used for treatment of anxiety, insomnia, drug addiction, mild infections, and pain. The aim of this study was to investigate the effect of a commercial extract of P. incarnata in the analgesia induced by alcohol withdrawal syndrome in rats. In addition, brain-derived neurotrophic factor and interleukin-10 levels were evaluated in prefrontal cortex, brainstem, and hippocampus. Male adult rats received by oral gavage: (1: water group) water for 19 days, 1 day interval and water (8 days); (2: P. incarnata group) water for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days); (3: alcohol withdrawal group) alcohol for 19 days, 1 day interval and water (8 days); and (4: P. incarnata in alcohol withdrawal) alcohol for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days). The tail-flick and hot plate tests were used as nociceptive response measures. Confirming previous study of our group, it was showed that alcohol-treated groups presented an increase in the nociceptive thresholds after alcohol withdrawal, which was reverted by P. incarnata, measured by the hot plate test. Besides, alcohol treatment increased brain-derived neurotrophic factor and interleukin-10 levels in prefrontal cortex, which was not reverted by P. incarnata. Considering these results, the P. incarnata treatment might be a potential therapy in the alcohol withdrawal syndrome. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Trajectories of social withdrawal and cognitive decline in the schizophrenia prodrome.

PubMed

Cullen, Kathryn; Guimaraes, Angela; Wozniak, Jeffrey; Anjum, Afshan; Schulz, S Charles; White, Tonya

2011-01-01

Schizophrenia is a heterogeneous neurodevelopmental disorder. Patients with high levels of negative symptoms have been identified as a specific subtype, but little is known about how the neurodevelopmental course may differ in this group. This study aimed to characterize developmental trajectories of premorbid social withdrawal and cognitive decline between patients with high versus low levels of negative symptoms in youth with schizophrenia-spectrum disorders. A standardized timeline was used to delineate the emergence of psychosis, social withdrawal, and cognitive decline in 52 subjects aged 8 to 19 with schizophrenia (n=36), schizophreniform (n=6), or schizoaffective disorder (n=10). The sample was divided into subgroups of high- (n=26) versus low- (n=26) negative symptoms, and developmental trajectories of premorbid symptoms were compared between groups. Mean ages for emergence of social withdrawal, cognitive decline, and psychosis were 11.1 years (SD=2.5), 11.9 (SD=4.4) and 13.2 years (SD=1.2), respectively. In the high-negative symptom group, the premorbid developmental trajectory for social withdrawal was more protracted. This group also had more severe cognitive decline at the onset of psychosis, but the premorbid trajectories for cognitive decline did not differ significantly between groups. This work documents a more severe and protracted trajectory of premorbid social withdrawal in patients with high levels of negative symptoms in comparison to those with low-negative symptoms. The findings reported here are supportive of the hypothesis that patients with illness characterized by high levels of negative symptoms may represent a subgroup with distinct neurodevelopmental abnormalities.

Effects of Functional Groups in Redox-Active Organic Molecules: A High-Throughput Screening Approach

DOE PAGES

Pelzer, Kenley M.; Cheng, Lei; Curtiss, Larry A.

2016-12-08

Nonaqueous redox flow batteries have attracted recent attention with their potential for high electrochemical storage capacity, with organic electrolytes serving as solvents with a wide electrochemical stability window. Organic molecules can also serve as electroactive species, where molecules with low reduction potentials or high oxidation potentials can provide substantial chemical energy. To identify promising electrolytes in a vast chemical space, high-throughput screening (HTS) of candidate molecules plays an important role, where HTS is used to calculate properties of thousands of molecules and identify a few organic molecules worthy of further attention in battery research. Here, in this work, we presentmore » reduction and oxidation potentials obtained from HTS of 4178 molecules. The molecules are composed of base groups of five- or six-membered rings with one or two functional groups attached, with the set of possible functional groups including both electron-withdrawing and electron-donating groups. In addition to observing the trends in potentials that result from differences in organic base groups and functional groups, we analyze the effects of molecular characteristics such as multiple bonds, Hammett parameters, and functional group position. In conclusion, this work provides useful guidance in determining how the identities of the base groups and functional groups are correlated with desirable reduction and oxidation potentials.« less

Effects of Functional Groups in Redox-Active Organic Molecules: A High-Throughput Screening Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pelzer, Kenley M.; Cheng, Lei; Curtiss, Larry A.

Nonaqueous redox flow batteries have attracted recent attention with their potential for high electrochemical storage capacity, with organic electrolytes serving as solvents with a wide electrochemical stability window. Organic molecules can also serve as electroactive species, where molecules with low reduction potentials or high oxidation potentials can provide substantial chemical energy. To identify promising electrolytes in a vast chemical space, high-throughput screening (HTS) of candidate molecules plays an important role, where HTS is used to calculate properties of thousands of molecules and identify a few organic molecules worthy of further attention in battery research. Here, in this work, we presentmore » reduction and oxidation potentials obtained from HTS of 4178 molecules. The molecules are composed of base groups of five- or six-membered rings with one or two functional groups attached, with the set of possible functional groups including both electron-withdrawing and electron-donating groups. In addition to observing the trends in potentials that result from differences in organic base groups and functional groups, we analyze the effects of molecular characteristics such as multiple bonds, Hammett parameters, and functional group position. In conclusion, this work provides useful guidance in determining how the identities of the base groups and functional groups are correlated with desirable reduction and oxidation potentials.« less

A modification of the Hammett equation for predicting ionisation constants of p-vinyl phenols.

PubMed

Sipilä, Julius; Nurmi, Harri; Kaukonen, Ann Marie; Hirvonen, Jouni; Taskinen, Jyrki; Yli-Kauhaluoma, Jari

2005-01-01

Currently there are several compounds used as drugs or studied as new chemical entities, which have an electron withdrawing group connected to a vinylic double bond in a phenolic or catecholic core structure. These compounds share a common feature--current computational methods utilizing the Hammett type equation for the prediction of ionisation constants fail to give accurate prediction of pK(a)'s for compounds containing the vinylic moiety. The hypothesis was that the effect of electron-withdrawing substituents on the pK(a) of p-vinyl phenols is due to the delocalized electronic structure of these compounds. Thus, this effect should be additive for multiple substituents attached to the vinylic double bond and quantifiable by LFER-based methods. The aim of this study was to produce an improved equation with a reduced tendency to underestimate the effect of the double bond on the ionisation of the phenolic hydroxyl. To this end a set of 19 para-substituted vinyl phenols was used. The ionisation constants were measured potentiometrically, and a training set of 10 compounds was selected to build a regression model (r2 = 0.987 and S.E. = 0.09). The average error with an external test set of six compounds was 0.19 for our model and 1.27 for the ACD-labs 7.0. Thus, we have been able to significantly improve the existing model for prediction of the ionisation constants of substituted p-vinyl phenols.

Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal.

PubMed

Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Wang, Yanlin; Liang, Wenmei

2017-08-02

Neurotrophins, brain-derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been implicated in the modulation of heroin dependency. This study was designed to explore the expression alterations of BDNF, NT-3, and NT-4 in the context of heroin dependence and withdrawal in the rat nucleus accumbens (NAc). Heroin dependence was induced by a progressive intraperitoneal treatment of heroin. The results showed that the expression levels of BDNF and NT-4 were significantly decreased in the NAc of rats with heroin addiction in comparison with the control group, whereas there was a significant increase in BDNF and NT-4 expressions in the groups of rats with both naloxone-induced and spontaneous withdrawal. Moreover, NT-3 expression was markedly increased in the NAc of rats with heroin addiction and spontaneous withdrawal in comparison with the control group, but decreased in the NAc of rats with naloxone-induced withdrawal. These results indicated that chronic administration of heroin results in the alterations of BDNF, NT-3, and NT-4 expressions in the rat NAc. BDNF, NT-3, and NT-4 may play a critical role in the development of heroin dependency and withdrawal.

Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal

PubMed Central

Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Wang, Yanlin

2017-01-01

Neurotrophins, brain-derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been implicated in the modulation of heroin dependency. This study was designed to explore the expression alterations of BDNF, NT-3, and NT-4 in the context of heroin dependence and withdrawal in the rat nucleus accumbens (NAc). Heroin dependence was induced by a progressive intraperitoneal treatment of heroin. The results showed that the expression levels of BDNF and NT-4 were significantly decreased in the NAc of rats with heroin addiction in comparison with the control group, whereas there was a significant increase in BDNF and NT-4 expressions in the groups of rats with both naloxone-induced and spontaneous withdrawal. Moreover, NT-3 expression was markedly increased in the NAc of rats with heroin addiction and spontaneous withdrawal in comparison with the control group, but decreased in the NAc of rats with naloxone-induced withdrawal. These results indicated that chronic administration of heroin results in the alterations of BDNF, NT-3, and NT-4 expressions in the rat NAc. BDNF, NT-3, and NT-4 may play a critical role in the development of heroin dependency and withdrawal. PMID:28538519

[Treatment of Alcohol Withdrawal Syndrome with Oxazepam or Clomethiazole - A Naturalistic Observational Study].

PubMed

Verthein, Uwe; Kuhn, Silke; Gabriel, Katrin; Mautsch, Ulrich; Reimer, Jens; Behrendt, Klaus

2018-03-01

Whilst internationally benzodiazepines are first choice for treatment of alcohol withdrawal syndrome, Germany has a long tradition with clomethiazole. This study explores effectiveness of clomethiazole versus oxazepam in the treatment of alcohol withdrawal syndrome within an observational, stratified, non-inferiority study in routine care. Main outcome criterion was severity of the alcohol withdrawal syndrome (Alcohol Withdrawal Syndrome [AWS]) Scale in the first five days. Additionally, the association between the detoxification protocol (five vs. ten days) and AWS-Score was examined. 453 patients (74.2 % male, average age 47.1 years [± 9.2]) took part; 249 received oxazepam (55.0 %) and 204 clomethiazole (45.0 %). The average duration of inpatient treatment was 14.0 days (± 6.3) in both groups. The average AWS-score was lower in the oxazepam group compared to the clomethiazole group (50.0 [± 26.5] vs. 56.2 [± 31.5]; p < .05; effect size d = - .25). Patients with a shorter detoxification protocol had a lower AWS sum score compared to patients with a longer protocol (p < .001; d = - .46). In treatment of alcohol withdrawal syndrome in routine care oxazepam yields at least comparable results to clomethiazole. © Georg Thieme Verlag KG Stuttgart · New York.

Impact of the voluntary withdrawal of over-the-counter cough and cold medications on pediatric ingestions reported to poison centers†

PubMed Central

Klein-Schwartz, Wendy; Sorkin, John David; Doyon, Suzanne

2015-01-01

SUMMARY Purpose To assess the impact of a voluntary withdrawal of over-the-counter cough and cold medications (OTC CCMs) labeled for children under age 2 years on pediatric ingestions reported to the American Association of Poison Control Centers. Methods Trend analysis of OTC CCMs ingestions in children under the age 6 years resulting from therapeutic errors or unintentional poisonings for 27 months before (pre-) and 15 months after (post-) the October 2007 voluntary withdrawal was conducted. The rates and outcome severity were examined. Results The mean annual rate of therapeutic errors involving OTC CCMs post-withdrawal, in children less than 2-years of age, 45.2/100 000 (95%CI 30.7–66.6) was 54% of the rate pre-withdrawal, 83.8/100 000 (95%CI 67.6–104.0). The decrease was statistically significant p < 0.02. In this age group, there was no difference in the frequency of severe outcomes resulting from therapeutic errors post-withdrawal. There was no significant difference in unintentional poisoning rates post-withdrawal 82.1/100 000 (66.0–102.2) vs. pre-withdrawal 98.3/100 000 (84.4–114.3) (p < 0.21) in children less than 2-years of age. There were no significant reductions in rates of therapeutic errors and unintentional poisonings in children ages 2–5 years, who were not targeted by the withdrawal. Conclusions A significant decrease in annual rates of therapeutic errors in children under 2-years reported to Poison Centers followed the voluntary withdrawal of OTC CCMs for children under age 2-years. Concerns that withdrawal of pediatric medications would paradoxically increase poisonings from parents giving products intended for older age groups to young children are not supported. PMID:20533537

Cyclopentadithiophene-Based Organic Semiconductors: Effect of Fluorinated Substituents on Electrochemical and Charge Transport Properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, J. Sreedhar; Kale, Tejaswini; Balaji, Ganapathy

2011-03-17

Thiophene-based semiconductors are often hole conductors that have been converted to electron-transporting materials by incorporation of electron-withdrawing groups at terminal positions, such as fluorinated substituents. This conversion of an otherwise p-type material to n-type material is often attributed to the lowering of the lowest unoccupied molecular orbital (LUMO) energy level due to the increased electron affinity in the molecule. Yet, it is not clear if lowering of LUMO energy level is a sufficient condition for yielding n-type material. Herein, we report small-molecule semiconductors based on cyclopentadithiophene (CPD), which can be orthogonally functionalized at two different positions, which allows us tomore » tune the frontier orbital energy levels. We find that simply lowering the LUMO energy level, without inclusion of fluoro groups, does not result in conversion of the otherwise p-type material to n-type material, whereas incorporation of fluorinated substituents does. This indicates that charge transport behavior is not an exclusive function of the frontier orbital energy levels.« less

Effective D-A-D type chromophore of fumaronitrile-core and terminal alkylated bithiophene for solution-processed small molecule organic solar cells.

PubMed

Nazim, M; Ameen, Sadia; Seo, Hyung-Kee; Shin, Hyung Shik

2015-06-12

A new and novel organic π-conjugated chromophore (named as RCNR) based on fumaronitrile-core acceptor and terminal alkylated bithiophene was designed, synthesized and utilized as an electron-donor material for the solution-processed fabrication of bulk-heterojunction (BHJ) small molecule organic solar cells (SMOSCs). The synthesized organic chromophore exhibited a broad absorption peak near green region and strong emission peak due to the presence of strong electron-withdrawing nature of two nitrile (-CN) groups of fumaronitrile acceptor. The highest occupied molecular orbital (HOMO) energy level of -5.82 eV and the lowest unoccupied molecular orbital (LUMO) energy level of -3.54 eV were estimated for RCNR due to the strong electron-accepting tendency of -CN groups. The fabricated SMOSC devices with RCNR:PC60BM (1:3, w/w) active layer exhibited the reasonable power conversion efficiency (PCE) of ~2.69% with high short-circuit current density (JSC) of ~9.68 mA/cm(2) and open circuit voltage (VOC) of ~0.79 V.

Effective D-A-D type chromophore of fumaronitrile-core and terminal alkylated bithiophene for solution-processed small molecule organic solar cells

PubMed Central

Nazim, M.; Ameen, Sadia; Seo, Hyung-Kee; Shin, Hyung Shik

2015-01-01

A new and novel organic π-conjugated chromophore (named as RCNR) based on fumaronitrile-core acceptor and terminal alkylated bithiophene was designed, synthesized and utilized as an electron-donor material for the solution-processed fabrication of bulk-heterojunction (BHJ) small molecule organic solar cells (SMOSCs). The synthesized organic chromophore exhibited a broad absorption peak near green region and strong emission peak due to the presence of strong electron-withdrawing nature of two nitrile (–CN) groups of fumaronitrile acceptor. The highest occupied molecular orbital (HOMO) energy level of –5.82 eV and the lowest unoccupied molecular orbital (LUMO) energy level of –3.54 eV were estimated for RCNR due to the strong electron-accepting tendency of –CN groups. The fabricated SMOSC devices with RCNR:PC60BM (1:3, w/w) active layer exhibited the reasonable power conversion efficiency (PCE) of ~2.69% with high short-circuit current density (JSC) of ~9.68 mA/cm2 and open circuit voltage (VOC) of ~0.79 V. PMID:26066557

Dissociation of protonated N-(3-phenyl-2H-chromen-2-ylidene)-benzenesulfonamide in the gas phase: cyclization via sulfonyl cation transfer.

PubMed

Wang, Shanshan; Dong, Cheng; Yu, Lian; Guo, Cheng; Jiang, Kezhi

2016-01-15

In the tandem mass spectrometry of protonated N-(3-phenyl-2H-chromen-2-ylidene)benzenesulfonamides, the precursor ions have been observed to undergo gas-phase dissociation via two competing channels: (a) the predominant channel involves migration of the sulfonyl cation to the phenyl C atom and the subsequent loss of benzenesulfinic acid along with cyclization reaction, and (b) the minor one involves dissociation of the precursor ion to give an ion/neutral complex of [sulfonyl cation/imine], followed by decomposition to afford sulfonyl cation or the INC-mediated electron transfer to give an imine radical cation. The proposed reaction channels have been supported by theoretical calculations and D-labeling experiments. The gas-phase cyclization reaction originating from the N- to C-sulfonyl cation transfer has been first reported to the best of our knowledge. For the substituted sulfonamides, the presence of electron-donating groups (R(2) -) at the C-ring effectively facilitates the reaction channel of cyclization reaction, whereas that of electron-withdrawing groups inhibits this pathway. Copyright © 2015 John Wiley & Sons, Ltd.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (5)--Six-month repeated oral dose toxicity study and supplement study in rats].

PubMed

Sameshima, H; Omori, M; Nishimura, Y; Chihaya, Y; Itoh, F; Mizushima, Y; Yabuuchi, K; Ohno, K; Furukawa, H; Yoshida, I; Ueno, M; Yahara, I; Kato, I

2001-05-01

Cefmatilen hydrochloride hydrate (S-1090) was orally administered to rats at dose levels of 100, 300 and 1000 mg potency/kg once daily for 6 months. All the S-1090 treated groups showed soft feces, reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet), abdominal distention, increased food and water consumption, lower urine pH, and a decrease of white blood cells counts (except for males of the 100 mg potency/kg group). One male in the 300 mg potency/kg group showed mucous feces and marked decrease in body weight, and diet in the middle stage of the administration period. In necropsy of the survivors of all treated groups, marked cecal enlargement was noted. No remarkable changes were observed in the other examination items. From the early stage of the withdrawal period, animals in the 1000 mg potency/kg group showed again soft or mucous feces and a marked decrease in body weight. Of these animals, one male died and another male was sacrificed in a moribund state at about 2 weeks of the withdrawal period. Enterocolitis was observed in these cases. Almost all animals recovered within 3 weeks of withdrawal. A supplemental study of the 6-month toxicity study was conducted to examine the mechanisms of enterocolitis and the changes observable in the 100 or 300 mg potency/kg groups after drug withdrawal. As a reference, cefdinir (CFDN), an oral cephem antibiotic the same as S-1090, was added in the 1000 mg potency/kg group. No deaths occurred in any groups. Decreased intestinal flora were noted in all the groups treated with S-1090 or CFDN at the end of the dosing period. At 2 weeks of the withdrawal period, C. difficile and its D-1 toxin in the cecal contents were highly detected in the S-1090 300 and 1000 mg potency/kg groups and CFDN group. Inflammatory changes in the cecum and colon were observed in these groups. At 4 weeks of the withdrawal period, intestinal flora in the S-1090 groups almost returned to the condition before dosing, but those in the CFDN group were retained highly. Cecal D-1 toxin in the CFDN group was positive and higher than in the S-1090 groups. It was thus considered that the critical condition with enterocolitis resulted from C. difficile, which proliferated more rapidly than the other bacteria and D-1 toxin produced by this bacteria in the withdrawal period. Above changes were commonly observed in the CFDN group. The NOAEL of S-1090 was assessed to be 100 mg potency/kg/day which induced no enteritis.

Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial.

PubMed

Rich, Josiah D; McKenzie, Michelle; Larney, Sarah; Wong, John B; Tran, Liem; Clarke, Jennifer; Noska, Amanda; Reddy, Manasa; Zaller, Nickolas

2015-07-25

Methadone is an effective treatment for opioid dependence. When people who are receiving methadone maintenance treatment for opioid dependence are incarcerated in prison or jail, most US correctional facilities discontinue their methadone treatment, either gradually, or more often, abruptly. This discontinuation can cause uncomfortable symptoms of withdrawal and renders prisoners susceptible to relapse and overdose on release. We aimed to study the effect of forced withdrawal from methadone upon incarceration on individuals' risk behaviours and engagement with post-release treatment programmes. In this randomised, open-label trial, we randomly assigned (1:1) inmates of the Rhode Island Department of Corrections (RI, USA) who were enrolled in a methadone maintenance-treatment programme in the community at the time of arrest and wanted to remain on methadone treatment during incarceration and on release, to either continuation of their methadone treatment or to usual care--forced tapered withdrawal from methadone. Participants could be included in the study only if their incarceration would be more than 1 week but less than 6 months. We did the random assignments with a computer-generated random permutation, and urn randomisation procedures to stratify participants by sex and race. Participants in the continued-methadone group were maintained on their methadone dose at the time of their incarceration (with dose adjustments as clinically indicated). Patients in the forced-withdrawal group followed the institution's standard withdrawal protocol of receiving methadone for 1 week at the dose at the time of their incarceration, then a tapered withdrawal regimen (for those on a starting dose >100 mg, the dose was reduced by 5 mg per day to 100 mg, then reduced by 3 mg per day to 0 mg; for those on a starting dose >100 mg, the dose was reduced by 3 mg per day to 0 mg). The main outcomes were engagement with a methadone maintenance-treatment clinic after release from incarceration and time to engagement with methadone maintenance treatment, by intention-to-treat and as-treated analyses, which we established in a follow-up interview with the participants at 1 month after their release from incarceration. Our study paid for 10 weeks of methadone treatment after release if participants needed financial help. This trial is registered with ClinicalTrials.gov, number NCT01874964. Between June 14, 2011, and April 3, 2013, we randomly assigned 283 prisoners to our study, 142 to continued methadone treatment, and 141 to forced withdrawal from methadone. Of these, 60 were excluded because they did not fit the eligibility criteria, leaving 114 in the continued-methadone group and 109 in the forced-withdrawal group (usual care). Participants assigned to continued methadone were more than twice as likely than forced-withdrawal participants to return to a community methadone clinic within 1 month of release (106 [96%] of 110 in the continued-methadone group compared with 68 [78%] of 87 in the forced-withdrawal group; adjusted hazard ratio [HR] 2·04, 95% CI 1·48-2·80). We noted no differences in serious adverse events between groups. For the continued-methadone and forced-withdrawal groups, the number of deaths were one and zero, non-fatal overdoses were one and two, admissions to hospital were one and four; and emergency-room visits were 11 and 16, respectively. Although our study had several limitations--eg, it only included participants incarcerated for fewer than 6 months, we showed that forced withdrawal from methadone on incarceration reduced the likelihood of prisoners re-engaging in methadone maintenance after their release. Continuation of methadone maintenance during incarceration could contribute to greater treatment engagement after release, which could in turn reduce the risk of death from overdose and risk behaviours. National Institute on Drug Abuse and the Lifespan/Tufts/Brown Center for AIDS Research from the National Institutes of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial

PubMed Central

Rich, Josiah D; McKenzie, Michelle; Larney, Sarah; Wong, John B; Tran, Liem; Clarke, Jennifer; Noska, Amanda; Reddy, Manasa; Zaller, Nickolas

2015-01-01

Summary Background Methadone is an effective treatment for opioid dependence. When people who are receiving methadone maintenance treatment for opioid dependence are incarcerated in prison or jail, most US correctional facilities discontinue their methadone treatment, either gradually, or more often, abruptly. This discontinuation can cause uncomfortable symptoms of withdrawal and renders prisoners susceptible to relapse and overdose on release. We aimed to study the effect of forced withdrawal from methadone upon incarceration on individuals’ risk behaviours and engagement with post-release treatment programmes. Methods In this randomised, open-label trial, we randomly assigned (1:1) inmates of the Rhode Island Department of Corrections (RI, USA) who were enrolled in a methadone maintenance-treatment programme in the community at the time of arrest and wanted to remain on methadone treatment during incarceration and on release, to either continuation of their methadone treatment or to usual care—forced tapered withdrawal from methadone. Participants could be included in the study only if their incarceration would be more than 1 week but less than 6 months. We did the random assignments with a computer-generated random permutation, and urn randomisation procedures to stratify participants by sex and race. Participants in the continued-methadone group were maintained on their methadone dose at the time of their incarceration (with dose adjustments as clinically indicated). Patients in the forced-withdrawal group followed the institution’s standard withdrawal protocol of receiving methadone for 1 week at the dose at the time of their incarceration, then a tapered withdrawal regimen (for those on a starting dose >100 mg, the dose was reduced by 5 mg per day to 100 mg, then reduced by 3 mg per day to 0 mg; for those on a starting dose ≤100 mg, the dose was reduced by 3 mg per day to 0 mg). The main outcomes were engagement with a methadone maintenance-treatment clinic after release from incarceration and time to engagement with methadone maintenance treatment, by intention-to-treat and as-treated analyses, which we established in a follow-up interview with the participants at 1 month after their release from incarceration. Our study paid for 10 weeks of methadone treatment after release if participants needed financial help. This trial is registered with ClinicalTrials.gov, number NCT01874964. Findings Between June 14, 2011, and April 3, 2013, we randomly assigned 283 prisoners to our study, 142 to continued methadone treatment, and 141 to forced withdrawal from methadone. Of these, 60 were excluded because they did not fit the eligibility criteria, leaving 114 in the continued-methadone group and 109 in the forced-withdrawal group (usual care). Participants assigned to continued methadone were more than twice as likely than forced-withdrawal participants to return to a community methadone clinic within 1 month of release (106 [96%] of 110 in the continued-methadone group compared with 68 [78%] of 87 in the forced-withdrawal group; adjusted hazard ratio [HR] 2·04, 95% CI 1·48–2·80). We noted no differences in serious adverse events between groups. For the continued-methadone and forced-withdrawal groups, the number of deaths were one and zero, non-fatal overdoses were one and two, admissions to hospital were one and four; and emergency-room visits were 11 and 16, respectively. Interpretation Although our study had several limitations—eg, it only included participants incarcerated for fewer than 6 months, we showed that forced withdrawal from methadone on incarceration reduced the likelihood of prisoners re-engaging in methadone maintenance after their release. Continuation of methadone maintenance during incarceration could contribute to greater treatment engagement after release, which could in turn reduce the risk of death from overdose and risk behaviours. PMID:26028120

Heterocyclic Schiff bases as non toxic antioxidants: Solvent effect, structure activity relationship and mechanism of action

NASA Astrophysics Data System (ADS)

Shanty, Angamaly Antony; Mohanan, Puzhavoorparambil Velayudhan

2018-03-01

Phenolic heterocyclic imine based Schiff bases from Thiophene-2-carboxaldehyde and Pyrrole-2-carboxaldehyde were synthesized and characterized as novel antioxidants. The solvent effects of these Schiff bases were determined and compared with standard antioxidants, BHA employing DPPH assay and ABTS assay. Fixed reaction time and Steady state measurement were used for study. IC50 and EC50 were calculated. Structure-activity relationship revealed that the electron donating group in the phenolic ring increases the activity where as the electron withdrawing moiety decreases the activity. The Schiff base derivatives showed antioxidant property by two different pathways namely SPLET and HAT mechanisms in DPPH assay. While in ABTS method, the reaction between ABTS radical and Schiff bases involves electron transfer followed by proton transfer (ET-PT) mechanism. The cytotoxicity of these compounds has been evaluated by MTT assay. The results showed that all these compounds are non toxic in nature.

A rhenium complex doped in a silica molecular sieve for molecular oxygen sensing: Construction and characterization.

PubMed

Yang, Xiaozhou; Li, Yanxiao

2016-01-15

This paper reported a diamine ligand and its Re(I) complex for potential application in oxygen sensing. The novelty of this diamine ligand localized at its increased conjugation chain which had a typical electron-withdrawing group of 1,3,4-oxadiazole. Electronic distribution of excited electrons and their lifetime were supposed to be increased, favoring oxygen sensing collision. This hypothesis was confirmed by single crystal analysis, theoretical calculation and photophysical measurement. It was found that this Re(I) complex had a long-lived emission peaking at 545 nm, favoring sensing application. By doping this complex into a silica matrix MCM-41, oxygen sensing performance and mechanism of the resulting composites were discussed in detail. Non-linear Stern-Volmer working curves were observed with maximum sensitivity of 5.54 and short response time of ~6 s. Copyright © 2015 Elsevier B.V. All rights reserved.

Single-molecular diodes based on opioid derivatives.

PubMed

Siqueira, M R S; Corrêa, S M; Gester, R M; Del Nero, J; Neto, A M J C

2015-12-01

We propose an efficient single-molecule rectifier based on a derivative of opioid. Electron transport properties are investigated within the non-equilibrium Green's function formalism combined with density functional theory. The analysis of the current-voltage characteristics indicates obvious diode-like behavior. While heroin presents rectification coefficient R>1, indicating preferential electronic current from electron-donating to electron-withdrawing, 3 and 6-acetylmorphine and morphine exhibit contrary behavior, R<1. Our calculations indicate that the simple inclusion of acetyl groups modulate a range of devices, which varies from simple rectifying to resonant-tunneling diodes. In particular, the rectification rations for heroin diodes show microampere electron current with a maximum of rectification (R=9.1) at very low bias voltage of ∼0.6 V and (R=14.3)∼1.8 V with resistance varying between 0.4 and 1.5 M Ω. Once most of the current single-molecule diodes usually rectifies in nanoampere, are not stable over 1.0 V and present electrical resistance around 10 M. Molecular devices based on opioid derivatives are promising in molecular electronics.

Stereotype Threat, Identification with Academics, and Withdrawal from School: Why the Most Successful Students of Colour Might Be Most Likely to Withdraw

ERIC Educational Resources Information Center

Osborne, Jason W.; Walker, Christopher

2006-01-01

Claude Steeles' stereotype threat hypothesis posits that when there are negative stereotypes about the intellectual capacity of certain (stigmatised) groups, members of that group suffer aversive consequences; group members who are most strongly identified with the stigmatised domain in question (e.g., intellectual or academic ability) are those…

Withdrawal-oriented therapy for smokers.

PubMed

Hajek, P

1989-06-01

The treatment approach of the Maudsley Hospital Smokers Clinic is described. It stems from the notion that smokers seeking help are dependent on nicotine, and that withdrawal discomfort is a major block to their success in quitting. Accordingly, therapy focuses on helping clients overcome nicotine deprivation. It uses nicotine replacement and a special format of group treatment. Details are given of preparation of clients, use of nicotine chewing gum, use of group-oriented groupwork, use of information about withdrawal, and training in withdrawal-oriented therapy. Data are presented concerning characteristics of the clientele, treatment adherence, and treatment results. A number of controversial issues are addressed, such as the optimal duration of treatment, timing of the quit date, the value of educational input, and the value of individualization of treatment goals.

Kratom abuse in Ramathibodi Poison Center, Thailand: a five-year experience.

PubMed

Trakulsrichai, Satariya; Tongpo, Achara; Sriapha, Charuwan; Wongvisawakorn, Sunun; Rittilert, Panee; Kaojarern, Sming; Wananukul, Winai

2013-01-01

Kratom (Mitragyna speciosa Korth), a native tree in Southeast Asia, is misused as an abuse drug and becomes legally widespread to several countries. Currently, it is available through the online market or by some shops. The clinical manifestations of Kratom's effects are not well-defined and the clinical studies are limited. This study was designed to identify the characteristics of Kratom poisoning and withdrawal cases from Kratom exposure cases in Ramathibodi Poison Center (RPC), Thailand, during a five-year period. We used a retrospective review of Kratom exposure cases from the RPC toxic surveillance system. A total of 52 Kratom exposure cases were identified. The trend of case consultations has been increasing. There were Kratom poisoning cases (76.9%) and withdrawal cases (23.1%). Common presenting symptoms in the poisoning group were palpitation (22.5%), followed by seizure (17.5%). For the withdrawal group, the common presenting symptoms were myalgia (33.3%), insomnia (16.67%), fatigue (16.67%), and chest discomfort (16.67%). There was a baby with withdrawal symptoms who was delivered from a chronic Kratom-abusing mother, suggesting possible exposure via the transplacental route. There were no deaths in either group. Kratom abuse can cause either poisoning or withdrawal. Most cases in both groups had good prognostic outcome.

Ab initio evaluation of the thermodynamic and electrochemical properties of alkyl halides and radicals and their mechanistic implications for atom transfer radical polymerization.

PubMed

Lin, Ching Yeh; Coote, Michelle L; Gennaro, Armando; Matyjaszewski, Krzysztof

2008-09-24

High-level ab initio molecular orbital calculations are used to study the thermodynamics and electrochemistry relevant to the mechanism of atom transfer radical polymerization (ATRP). Homolytic bond dissociation energies (BDEs) and standard reduction potentials (SRPs) are reported for a series of alkyl halides (R-X; R = CH 2CN, CH(CH 3)CN, C(CH 3) 2CN, CH 2COOC 2H 5, CH(CH 3)COOCH 3, C(CH 3) 2COOCH 3, C(CH 3) 2COOC 2H 5, CH 2Ph, CH(CH 3)Ph, CH(CH 3)Cl, CH(CH 3)OCOCH 3, CH(Ph)COOCH 3, SO 2Ph, Ph; X = Cl, Br, I) both in the gas phase and in two common organic solvents, acetonitrile and dimethylformamide. The SRPs of the corresponding alkyl radicals, R (*), are also examined. The computational results are in a very good agreement with the experimental data. For all alkyl halides examined, it is found that, in the solution phase, one-electron reduction results in the fragmentation of the R-X bond to the corresponding alkyl radical and halide anion; hence it may be concluded that a hypothetical outer-sphere electron transfer (OSET) in ATRP should occur via concerted dissociative electron transfer rather than a two-step process with radical anion intermediates. Both the homolytic and heterolytic reactions are favored by electron-withdrawing substituents and/or those that stabilize the product alkyl radical, which explains why monomers such as acrylonitrile and styrene require less active ATRP catalysts than vinyl chloride and vinyl acetate. The rate constant of the hypothetical OSET reaction between bromoacetonitrile and Cu (I)/TPMA complex was estimated using Marcus theory for the electron-transfer processes. The estimated rate constant k OSET = approximately 10 (-11) M (-1) s (-1) is significantly smaller than the experimentally measured activation rate constant ( k ISET = approximately 82 M (-1) s (-1) at 25 degrees C in acetonitrile) for the concerted atom transfer mechanism (inner-sphere electron transfer, ISET), implying that the ISET mechanism is preferred. For monomers bearing electron-withdrawing groups, the one-electron reduction of the propagating alkyl radical to the carbanion is thermodynamically and kinetically favored over the one-electron reduction of the corresponding alkyl halide unless the monomer bears strong radical-stabilizing groups. Thus, for monomers such as acrylates, catalysts favoring ISET over OSET are required in order to avoid chain-breaking side reactions.

Synthesis and solar-cell applications of novel furanyl-substituted anthracene derivatives

NASA Astrophysics Data System (ADS)

Kivrak, Arif; Er, Ömer Faruk; Kivrak, Hilal; Topal, Yasemin; Kuş, Mahmut; Çamlısoy, Yesim

2017-11-01

At present, novel furanyl-substituted anthracene derivatives; namely 9,10-di(furan-2-yl)anthracene (DFA), 5,5‧-(anthracene-9,10-diyl)bis(furan-2-carbaldehyde) (DAFA) and 2,2‧-((5,5‧-(anthracene-9,10-diyl)bis(furan-5,2-diyl))bis(methanylylidene))dimalononitrile (DCNFA) were designed and synthesized successfully by employing Stille Cross-Coupling, Vilsmeier-Haack and Knoevenagel condensation reactions, respectively. This methodology provides a practical new route for the synthesis of furanyl-substituted anthracene derivatives bearing strong electron-withdrawing groups. The electrochemical and electro-optical properties of these novel furanyl-substituted anthracene derivatives were also examined with strong acceptor-π-donor-π-acceptor interactions. Furthermore, Highest occupied molecular orbital (HOMO), Lowest Unoccupied molecular orbital (LUMO), and band gap (Eg) values were investigated by using spectroscopic methods. Electrochemical and electro-optical properties were calculated and compared to DFA, DAFA and DCNFA. Eg was found as 2.85, 2.71, and 2.33 eV, respectively. Consequently, Organic Solar Cells (OSC) were fabricated to investigate their solar cell performances. The strong electron withdrawing groups did not increase the solar cell performance of furanyl-anthracenes. Surprisingly, DFA was found to exhibit the best OSCs performance (Efficiency = 3.36). As a result, one could note that these novel furanyl-substituted anthracene derivatives are good candidate for the applications of the OSCs. Our results might help in the development of new materials with important electrochemical functions by giving the advantage of designing and further derivatization of new generation small organic molecules for photovoltaic device applications.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.; Xu, J.

1999-04-06

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth; Xu, Jide

1999-01-01

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity.

Substituent effects on furan-phenylene copolymer for photovoltaic improvement: A density functional study

NASA Astrophysics Data System (ADS)

Janprapa, Nuttaporn; Vchirawongkwin, Viwat; Kritayakornupong, Chinapong

2018-06-01

The structural, electronic and photovoltaic properties of furan-phenylene copolymer ((Fu-co-Ph)4) and its derivatives were evaluated using density functional theory (DFT) and time-dependent density functional theory (TD-DFT). The calculated band gaps of pristine furan and phenylene are in good agreement with the available experimental data. The lower band gap value of 2.72 eV was obtained from -NO2 and -NHCH3 substituents, leading to broader solar absorption range. With respected to the reorganization energy, -OCH3, -NHCH3, -OH, -SCH3, -CH3, -CF3, -NO2, and -F substituted (Fu-co-Ph)4 structures were classified as better electron donor materials. For combination with PC61BM, -NO2, -CN, -CF3 and -F functionalized copolymers demonstrated significantly higher open circuit voltage (Voc) values ranging from 1.07 to 2.10 eV. Our results revealed that electron withdrawing group substitution on furan-phenylene copolymers was an effective way for improving electronic and optical properties of donor materials used in photovoltaic applications.

NOSH-Aspirin Inhibits Colon Cancer Cell Growth: Effects Of Positional Isomerism.

PubMed

Vannini, Federica; Kodela, Ravinder; Chattopadhyay, Mitali; Kashfi, Khosrow

2015-08-01

NOSH-aspirin, a novel hybrid that releases nitric oxide (NO) and hydrogen sulfide (H 2 S) was designed to overcome the potential side effects of aspirin. We compared the cell growth inhibitory properties of ortho-, meta-, and para-NOSH-aspirins. Effects of electron donating/withdrawing groups on the stability and biological activity of these novel compounds were also evaluated. Cell line: HT-29 (Cyclooxygenase, COX-1 & -2 expressing) and HCT 15 (COX null) human colon adenocarcimoa; Cell growth: MTT; Cell cycle phase distribution: Flow cytometry; Apoptosis: subdiploid (sub-G 0 /G 1 ) peak in DNA content histograms; Proliferation: PCNA; ROS: measured hydrogen peroxide and super oxide by flow cytometry using DCFDA and DHE dyes. The IC 50 s for growth inhibition in µM at 24h were, HT-29: ortho-NOSH-ASA (0.04±0.011), meta-NOSH-ASA (0.24±0.11), para-NOSH-ASA (0.46±0.17); significance between the groups were: o vs m P>0.05, o vs p P<0.05, m vs p P>0.05; HCT 15: ortho-NOSH-ASA (0.062±0.006), meta-NOSH-ASA (0.092±0.004), para-NOSH-ASA (0.37±0.04); significance between the groups were: o vs m P<0.01, o vs p P<0.001, m vs p P<0.001. Electron donating/withdrawing groups significantly affected these IC 50 s. All positional isomers qualitatively had similar effects on proliferation, apoptosis, and caused G 0 /G 1 cell cycle arrest in both colon cancer cell lines. The underlying mechanism for these observations appeared to be mediated through ROS, as pretreatment of the cells with N-acetylcysteine, partially blocked these effects. Positional isomerism affects the potency of NOSH-aspirin. The effects appear to be COX independent. Copyright © 2015. Published by Elsevier B.V.

Organic sensitizers from D-π-A to D-A-π-A: effect of the internal electron-withdrawing units on molecular absorption, energy levels and photovoltaic performances.

PubMed

Wu, Yongzhen; Zhu, Weihong

2013-03-07

The high performance and low cost of dye-sensitized solar cells (DSSCs) have drawn great interest from both academic and industrial circles. The research on exploring novel efficient sensitizers, especially on inexpensive metal-free pure organic dyes, has never been suspended. The donor-π bridge-acceptor (D-π-A) configuration is mainstream in the design of organic sensitizers due to its convenient modulation of the intramolecular charge-transfer nature. Recently, it has been found that incorporation of additional electron-withdrawing units (such as benzothiadiazole, benzotriazole, quinoxaline, phthalimide, diketopyrrolopyrrole, thienopyrazine, thiazole, triazine, cyanovinyl, cyano- and fluoro-substituted phenyl) into the π bridge as internal acceptors, termed the D-A-π-A configuration, displays several advantages such as tuning of the molecular energy levels, red-shift of the charge-transfer absorption band, and distinct improvement of photovoltaic performance and stability. We apply the D-A-π-A concept broadly to the organic sensitizers containing additional electron-withdrawing units between electron donors and acceptors. This review is projected to summarize the category of pure organic sensitizers on the basis of the D-A-π-A feature. By comparing the structure-property relationship of typical photovoltaic D-A-π-A dyes, the important guidelines in the design of such materials are highlighted.

Hydrophobic ionic liquids

DOEpatents

Koch, V.R.; Nanjundiah, C.; Carlin, R.T.

1998-10-27

Ionic liquids having improved properties for application in non-aqueous batteries, electrochemical capacitors, electroplating, catalysis and chemical separations are disclosed. Exemplary compounds have one of the following formulas shown in a diagram wherein R{sub 1}, R{sub 2}, R{sub 3}, R{sub 4}, R{sub 5}, and R{sub 6} are either H; F; separate alkyl groups of from 1 to 4 carbon atoms, respectively, or joined together to constitute a unitary alkylene radical of from 2 to 4 carbon atoms forming a ring structure converging on N; or separate phenyl groups; and wherein the alkyl groups, alkylene radicals or phenyl groups may be substituted with electron withdrawing groups, preferably F-, Cl-, CF{sub 3}-, SF{sub 5}-, CF{sub 3}S-, (CF{sub 3}){sub 2}CHS- or (CF{sub 3}){sub 3}CS-; and X{sup {minus}} is a non-Lewis acid-containing polyatomic anion having a van der Waals volume exceeding 100 {angstrom}{sup 3}. 4 figs.

Hydrophobic ionic liquids

DOEpatents

Koch, Victor R.; Nanjundiah, Chenniah; Carlin, Richard T.

1998-01-01

Ionic liquids having improved properties for application in non-aqueous batteries, electrochemical capacitors, electroplating, catalysis and chemical separations are disclosed. Exemplary compounds have one of the following formulas: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are either H; F; separate alkyl groups of from 1 to 4 carbon atoms, respectively, or joined together to constitute a unitary alkylene radical of from 2 to 4 carbon atoms forming a ring structure converging on N; or separate phenyl groups; and wherein the alkyl groups, alkylene radicals or phenyl groups may be substituted with electron withdrawing groups, preferably F--, Cl--, CF.sub.3 --, SF.sub.5 --, CF.sub.3 S--, (CF.sub.3).sub.2 CHS-- or (CF.sub.3).sub.3 CS--; and X.sup.- is a non-Lewis acid-containing polyatomic anion having a van der Waals volume exceeding 100 .ANG..sup.3.

Trajectories of abstinence-induced Internet gaming withdrawal symptoms: A prospective pilot study.

PubMed

Kaptsis, Dean; King, Daniel L; Delfabbro, Paul H; Gradisar, Michael

2016-12-01

Internet Gaming Disorder (IGD) is positioned in the appendix of the DSM-5 as a condition requiring further study. The IGD criteria refer to withdrawal symptoms, including irritability, anxiety, or sadness, that follow cessation of Internet gaming (APA, 2013). The aim of this study was to prospectively examine the nature of Internet gaming withdrawal symptoms, if they occur, under gaming abstinence conditions. This study employed a repeated-measures protocol to examine the cognitive-affective reactions of participants undertaking an 84-h Internet gaming abstinence period. The sample included individuals who met the IGD criteria as well as those who regularly played Internet games but did not meet the IGD criteria. Outcome variables included affect (positive and negative), psychological distress (depression, anxiety, stress), and Internet gaming withdrawal symptoms (craving/urge, thoughts about gaming, inability to resist gaming). A total of 24 participants ( M age  = 24.6 years, SD  = 5.8) were recruited from online gaming communities, and completed a series of online surveys before, during, and after abstaining from Massively Multiplayer Online (MMO) games. Both the IGD group and the non-IGD group experienced an abstinence-induced decline in withdrawal symptomatology, negative affect, and psychological distress. The IGD group experienced its largest decline in withdrawal symptomatology within the first 24 h of abstinence. These preliminary data suggest that gaming withdrawal symptoms may follow, at least initially, negative linear and quadratic trends. Further prospective work in larger samples involving longer periods of abstinence is required to verify and expand upon these observations.

Acute exercise effects on smoking withdrawal symptoms and desire to smoke are not related to expectation.

PubMed

Daniel, James Z; Cropley, Mark; Fife-Schaw, Chris

2007-11-01

Recent research has shown that 10 min of moderate intensity exercise reduce smoking withdrawal symptoms and desire to smoke in acutely abstinent smokers. The aim of the current study was to determine whether the reductions are related to participant expectation of these effects. Forty-five sedentary participants who had smoked ten or more cigarettes per day for at least 3 years reported their expectation of the effects of exercise on smoking withdrawal symptoms. Approximately 1 month later, participants were randomly assigned to one of three groups after 11-15 h of overnight smoking abstinence. Each group read either a positive, negative or neutral statement concerning exercise effects on smoking withdrawal symptoms. They rated their expectation again and then completed 10 min of moderate intensity exercise on a stationary bicycle ergometer. Using standardised scales, participants rated smoking withdrawal symptoms and desire to smoke at 10, 5 and 0 min before exercise, then at 5 and 10 min during exercise and 15 and 20 min post-exercise. Expectation of exercise effects on withdrawal were manipulated in the predicted directions. No significant group main effects were found for any symptom. Significant reductions in symptoms and desire to smoke occurred during and after exercise regardless of participant expectation. Ten minutes of moderate intensity exercise can lead to reductions in desire to smoke and smoking withdrawal symptoms, which are not due to the participant's expectation of exercise effects. These findings support the use of short periods of exercise as an aid to smoking cessation.

Effect of the Phosphine Steric and Electronic Profile on the Rh-Promoted Dehydrocoupling of Phosphine–Boranes

PubMed Central

2014-01-01

The electronic and steric effects in the stoichiometric dehydrocoupling of secondary and primary phosphine–boranes H3B·PR2H [R = 3,5-(CF3)2C6H3; p-(CF3)C6H4; p-(OMe)C6H4; adamantyl, Ad] and H3B·PCyH2 to form the metal-bound linear diboraphosphines H3B·PR2BH2·PR2H and H3B·PRHBH2·PRH2, respectively, are reported. Reaction of [Rh(L)(η6-FC6H5)][BArF4] [L = Ph2P(CH2)3PPh2, ArF = 3,5-(CF3)2C6H3] with 2 equiv of H3B·PR2H affords [Rh(L)(H)(σ,η-PR2BH3)(η1-H3B·PR2H)][BArF4]. These complexes undergo dehydrocoupling to give the diboraphosphine complexes [Rh(L)(H)(σ,η2-PR2·BH2PR2·BH3)][BArF4]. With electron-withdrawing groups on the phosphine–borane there is the parallel formation of the products of B–P cleavage, [Rh(L)(PR2H)2][BArF4], while with electron-donating groups no parallel product is formed. For the bulky, electron rich, H3B·P(Ad)2H no dehydrocoupling is observed, but an intermediate Rh(I) σ phosphine–borane complex is formed, [Rh(L){η2-H3B·P(Ad)2H}][BArF4], that undergoes B–P bond cleavage to give [Rh(L){η1-H3B·P(Ad)2H}{P(Ad)2H}][BArF4]. The relative rates of dehydrocoupling of H3B·PR2H (R = aryl) show that increasingly electron-withdrawing substituents result in faster dehydrocoupling, but also suffer from the formation of the parallel product resulting from P–B bond cleavage. H3B·PCyH2 undergoes a similar dehydrocoupling process, and gives a mixture of stereoisomers of the resulting metal-bound diboraphosphine that arise from activation of the prochiral P–H bonds, with one stereoisomer favored. This diastereomeric mixture may also be biased by use of a chiral phosphine ligand. The selectivity and efficiencies of resulting catalytic dehydrocoupling processes are also briefly discussed. PMID:24617924

Structure-Property Relationship of Phenylene-Based Self-Assembled-Monolayers for Record Low Work Function of Indium Tin Oxide.

PubMed

Benneckendorf, Frank S; Hillebrandt, Sabina; Ullrich, Florian; Rohnacher, Valentina; Hietzschold, Sebastian; Jänsch, Daniel; Freudenberg, Jan; Beck, Sebastian; Mankel, Eric; Jaegermann, Wolfram; Pucci, Annemarie; Bunz, Uwe H F; Müllen, Klaus

2018-06-20

Studying the structure-property relations of tailored dipolar phenyl and biphenylphosphonic acids we report self-assembled monolayers with a significant decrease of the work function (WF) of indium-tin oxide (ITO) electrodes. While the strengths of the dipoles are varied through the different molecular lengths and the introduction of electron-withdrawing fluorine atoms, the surface energy is kept constant through the electron-donating N,N dimethylamine head groups. The self-assembled monolayer formation and its modification of the electrodes are investigated via infrared reflection absorption spectroscopy, contact angle measurements, and photoelectron spectroscopy. The WF decrease of ITO correlates with increasing molecular dipoles. The lowest ever recorded WF of 3.7 eV is achieved with the fluorinated biphenylphosphonic acid.

Neural correlates of social approach and withdrawal in patients with major depression.

PubMed

Derntl, Birgit; Seidel, Eva-Maria; Eickhoff, Simon B; Kellermann, Thilo; Gur, Ruben C; Schneider, Frank; Habel, Ute

2011-01-01

Successful human interaction is based on correct recognition, interpretation, and appropriate reaction to facial affect. In depression, social skill deficits are among the most restraining symptoms leading to social withdrawal, thereby aggravating social isolation and depressive affect. Dysfunctional approach and withdrawal tendencies to emotional stimuli have been documented, but the investigation of their neural underpinnings has received limited attention. We performed an fMRI study including 15 depressive patients and 15 matched, healthy controls. All subjects performed two tasks, an implicit joystick task as well as an explicit rating task, both using happy, neutral, and angry facial expressions. Behavioral data analysis indicated a significant group effect, with depressed patients showing more withdrawal than controls. Analysis of the functional data revealed significant group effects for both tasks. Among other regions, we observed significant group differences in amygdala activation, with patients showing less response particularly during approach to happy faces. Additionally, significant correlations of amygdala activation with psychopathology emerged, suggesting that more pronounced symptoms are accompanied by stronger decreases of amygdala activation. Hence, our results demonstrate that depressed patients show dysfunctional social approach and withdrawal behavior, which in turn may aggravate the disorder by negative social interactions contributing to isolation and reinforcing cognitive biases.

Protic NNN and NCN Pincer-Type Ruthenium Complexes Featuring (Trifluoromethyl)pyrazole Arms: Synthesis and Application to Catalytic Hydrogen Evolution from Formic Acid.

PubMed

Nakahara, Yoshiko; Toda, Tatsuro; Matsunami, Asuka; Kayaki, Yoshihito; Kuwata, Shigeki

2018-01-04

NNN and NCN pincer-type ruthenium(II) complexes featuring two protic pyrazol-3-yl arms with a trifluoromethyl (CF 3 ) group at the 5-position were synthesized and structurally characterized to evaluate the impact of the substitution on the properties and catalysis. The increased Brønsted acidity by the highly electron-withdrawing CF 3 pendants was demonstrated by protonation-deprotonation experiments. By contrast, the IR spectra of the carbonyl derivatives as well as the cyclic voltammogram indicated that the electron density of the ruthenium atom is negligibly influenced by the CF 3 group. Catalysis of these complexes in the decomposition of formic acid to dihydrogen and carbon dioxide was also examined. The NNN pincer-type complex 1 a with the CF 3 group exhibited a higher catalytic activity than the tBu-substituted analogue 1 b. In addition, the bis(CF 3 -pyrazolato) ammine derivative 4 catalyzed the reaction even in the absence of base additives. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of the physicochemical and aromatic properties on the chemical reactivity and its relation with carcinogenic and anticoagulant effect of 17β-aminoestrogens

NASA Astrophysics Data System (ADS)

Soriano-Correa, Catalina; Raya, Angélica; Barrientos-Salcedo, Carolina; Esquivel, Rodolfo O.

2014-06-01

Activity of steroid hormones is dependent upon a number of factors, as solubility, transport and metabolism. The functional differences caused by structural modifications could exert an influence on the chemical reactivity and biological effect. The goal of this work is to study the influence of the physicochemical and aromatic properties on the chemical reactivity and its relation with the carcinogenic risk that can associate with the anticoagulant effect of 17β-aminoestrogens using quantum-chemical descriptors at the DFT-B3LYP, BH&HLYP and M06-2X levels. The relative acidity of (H1) of the hydroxyl group increases with electron-withdrawing groups. Electron-donor groups favor the basicity. The steric hindrance of the substituents decreases the aromatic character and consequently diminution the carcinogenic effect. Density descriptors: hardness, electrophilic index, atomic charges, molecular orbitals, electrostatic potential and their geometric parameters permit analyses of the chemical reactivity and physicochemical features and to identify some reactive sites of 17β-aminoestrogens.

EPR and pulsed ENDOR study of intermediates from reactions of aromatic azides with group 13 metal trichlorides

PubMed Central

Bencivenni, Giorgio; Cesari, Riccardo; Nanni, Daniele; El Mkami, Hassane

2010-01-01

Summary The reactions of group 13 metal trichlorides with aromatic azides were examined by CW EPR and pulsed ENDOR spectroscopies. Complex EPR spectra were obtained from reactions of aluminium, gallium and indium trichlorides with phenyl azides containing a variety of substituents. Analysis of the spectra showed that 4-methoxy-, 3-methoxy- and 2-methoxyphenyl azides all gave ‘dimer’ radical cations [ArNHC6H4NH2]+• and trimers [ArNHC6H4NHC6H4NH2]+• followed by polymers. 4-Azidobenzonitrile, with its electron-withdrawing substituent, did not react. In general the aromatic azides appeared to react most rapidly with AlCl3 but this reagent tended to generate much polymer. InCl3 was the least reactive group 13 halide. DFT computations of the radical cations provided corroborating evidence and suggested that the unpaired electrons were accommodated in extensive π-delocalised orbitals. A mechanism to account for the reductive conversion of aromatic azides to the corresponding anilines and thence to the dimers and trimers is proposed. PMID:21049080

Mechanisms for the adsorption of substituted nitrobenzenes by smectite clays.

PubMed

Boyd, S A; Sheng, G; Teppen, B J; Johnston, C T

2001-11-01

To more fully understand the potential for transport of nitroaromatic compounds in soils and subsoils,the adsorption of a series of para- and meta-substituted nitrobenzenes (SNBs) by K-smectite clay was measured. Adsorption isotherms were fit to the Freundlich equation, and the resultant Freundlich adsorption coefficients (log(Kf) were positively correlated with the Hammett substituent constant (r2 = 0.80). This relationship and a positive reaction constant (p = 1.15) indicate that the adsorption reaction is favored by electron-withdrawing substituents. These results are consistent with an electron donor (smectite)-acceptor (substituted nitrobenzene) mechanism offered previously. However, quantum calculations did not reveal any systematic relationship between the Hammett constant and the electron density on the aromatic ring, which would explain a donor-acceptor relationship. Rather, electron density donated by a second substituent on nitrobenzene appears to be appropriated by the nitro group leaving ring electron density unchanged. Fourier transform infrared spectroscopy revealed shifts in the -NO2 vibrational modes of 1,3,5-trinitrobenzene (TNB) upon adsorption to K+-smectite that were consistent with the complexation of K+ by -NO2 groups. Such TNB vibrational shifts were not observed for SWy-1 saturated with more strongly hydrated cations (i.e., Na+, Mg2+, Ca2+, and Ba2+). The simultaneous interaction of multiple -NO2 groups with exchangeable K+ was indicated by molecular dynamic simulations. Adsorption of SNBs by smectite clays appears to result from the additive interactions of -NO2 groups and secondary substituents with interlayer K+ ions. Adsorption occurs to a greater or lesser extent depending on the abilities of substituents to complex additional interlayer cations and the water solubilities of SNBs. We conclude that the adsorption trends of SNBs on K-SAz-1 can be explained without recourse to hypothetical electron donor-acceptor complexes.

EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study.

PubMed

Caponnetto, Pasquale; Campagna, Davide; Cibella, Fabio; Morjaria, Jaymin B; Caruso, Massimo; Russo, Cristina; Polosa, Riccardo

2013-01-01

Electronic cigarettes (e-cigarettes) are becoming increasingly popular with smokers worldwide. Users report buying them to help quit smoking, to reduce cigarette consumption, to relieve tobacco withdrawal symptoms, and to continue having a 'smoking' experience, but with reduced health risks. Research on e-cigarettes is urgently needed in order to ensure that the decisions of regulators, healthcare providers and consumers are based on science. Methods ECLAT is a prospective 12-month randomized, controlled trial that evaluates smoking reduction/abstinence in 300 smokers not intending to quit experimenting two different nicotine strengths of a popular e-cigarette model ('Categoria'; Arbi Group Srl, Italy) compared to its non-nicotine choice. GroupA (n = 100) received 7.2 mg nicotine cartridges for 12 weeks; GroupB (n = 100), a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges; GroupC (n = 100) received no-nicotine cartridges for 12 weeks. The study consisted of nine visits during which cig/day use and exhaled carbon monoxide (eCO) levels were measured. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed. Declines in cig/day use and eCO levels were observed at each study visits in all three study groups (p<0.001 vs baseline), with no consistent differences among study groups. Smoking reduction was documented in 22.3% and 10.3% at week-12 and week-52 respectively. Complete abstinence from tobacco smoking was documented in 10.7% and 8.7% at week-12 and week-52 respectively. A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study. Participants' perception and acceptance of the product under investigation was satisfactory. In smokers not intending to quit, the use of e-cigarettes, with or without nicotine, decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects. ClinicalTrials.gov NCT01164072 NCT01164072.

Effectiveness of Stress Management Skill Training on the Depression, Anxiety and Stress Levels in Drug Addicts after Drug Withdrawal

PubMed Central

Habibi, Zahra; Tourani, Somayeh; Sadeghi, Hasan; Abolghasemi, Abbass

2013-01-01

Background Stressful life events may cause initiation of drug use among people. The main purpose of this study was to evaluate the effectiveness of stress management skill training on depression, anxiety and stress levels in drug addicts after withdrawal. Objectives The population included all drug addicts after withdrawal in 2012 in Alborz province. Materials and Methods The study was quasi-experimental with pretest-posttest design with a control group. Levels of emotional reactions (depression, anxiety and stress) in all referrals to a counseling center for drug withdrawal in 2012 using the Depression, Anxiety, Stress (DASS-21) questionnaire was assessed. The study population included drug addicts after withdrawal. The sampling method was available sampling and random assignment. Thirty people who had higher emotional reactions were randomly selected and divided into two test (n = 15) and control (n = 15) groups. For the test group, a stress management skill training course was held in twelve 90-minute sessions, but the control group received no intervention. The obtained data were analyzed using SPSS-19 software with analysis of covariance. Results The results showed that stress management skill training has a significant effect on reducing emotional reactions (P < 0.01). It was noted that after 2 months test group follow-up, stress management training has retained its effect. Conclusion Apparently, training addicts about life skills, particularly stress management seems to be a good idea. PMID:24971280

Caffeine dependence in rats: effects of exposure duration and concentration.

PubMed

Dingle, Rachel N; Dreumont-Boudreau, Sarah E; Lolordo, Vincent M

2008-09-03

Groups of rats were chronically exposed to a 1.0-g/L caffeine solution for 5, 10, 15 or 20 days. Upon removal of caffeine, rats were given brief exposure to a novel flavour CS (withdrawal CS) followed by 12 days of plain water and then brief exposure to a second flavour CS (neutral CS). Only rats exposed to 20 days of caffeine strongly preferred the neutral CS to the withdrawal CS in a 2-bottle test. In Experiment 2, groups of rats were chronically exposed to caffeine at one of four concentrations (1.0, 0.5, 0.25, or 0.125 g/L) for 21 days, after which withdrawal and neutral CSs were established. Only rats that drank the highest caffeine concentration, 1.0 g/L, preferred the neutral CS to the withdrawal CS. This suggests that long exposure to a strong caffeine solution is required in order to induce dependence in rats such that a CS associated with the withdrawal of caffeine becomes avoided.

Pharmacological therapies for management of opium withdrawal.

PubMed

Rahimi-Movaghar, Afarin; Gholami, Jaleh; Amato, Laura; Hoseinie, Leila; Yousefi-Nooraie, Reza; Amin-Esmaeili, Masoumeh

2018-06-21

Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium. To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal. We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials. Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days. We used the standard methodological procedures expected by Cochrane. We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low.When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day.Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1 study, very low-quality evidence); clonidine versus clonidine plus amantadine (RR 1.03, 95% CI 0.86 to 1.24; 69 participants, 1 study); clonidine versus buprenorphine in an inpatient setting (RR 1.04, 95% CI 0.90 to 1.20; 1 study, 35 participants, very low-quality evidence); methadone versus tramadol (RR 0.95, 95% CI 0.65 to 1.37; 1 study, 72 participants, very low-quality evidence); methadone versus methadone plus gabapentin (RR 1.17, 95% CI 0.96 to 1.43; 1 study, 40 participants, low-quality evidence), and tincture of opium versus methadone (1 study, 74 participants, low-quality evidence).Comparing different pharmacological treatments with each other, adding amantadine to clonidine decreased withdrawal scores rated at day 3 (mean difference (MD) -3.56, 95% CI -5.97 to -1.15; 1 study, 60 participants, very low-quality evidence). Comparing clonidine with buprenorphine in an inpatient setting, we found no difference in withdrawal symptoms rated by a physician (MD -1.40, 95% CI -2.93 to 0.13; 1 study, 34 participants, very low-quality evidence), and results in favour of buprenorpine when rated by participants (MD -11.80, 95% CI -15.56 to -8.04). Buprenorphine was superior to clonidine in controlling severe withdrawal symptoms in an outpatient setting (RR 0.35, 95% CI 0.19 to 0.64; 1 study, 76 participants). We found no difference in the comparison of methadone versus tramadol (MD 0.04, 95% CI -2.68 to 2.76; 1 study, 72 participants) and in the comparison of methadone versus methadone plus gabapentin (MD -2.20, 95% CI -6.72 to 2.32; 1 study, 40 participants).Comparing clonidine versus buprenorphine in an outpatient setting, more adverse effects were reported in the clonidine group (1 study, 76 participants). Higher numbers of participants in the clonidine group experienced hypotension at days 5 to 8, headache at days 1 to 8, sedation at days 5 to 8, dizziness and dry mouth at days 1 to 10, and nausea at days 1 to 9. Sweating was reported in a significantly higher number of participants in the buprenorphine group at days 1 to 10. We found no difference between groups for all the other comparisons considering this outcome.Comparing different dosages of the same pharmacological detoxification treatment, a high dose of clonidine (1 to 1.2 mg/day) did not differ from a low dose of clonidine (0.5 to 0.6 mg/day) in completion of treatment in an inpatient setting (RR 1.00, 95% CI 0.84 to 1.19; 1 study, 68 participants), however a higher number of participants with hypotension was reported in the high-dose group (RR 3.25, 95% CI 1.77 to 5.98). Gradual reduction of methadone was associated with more adverse effects than abrupt withdrawal of methadone (RR 2.25, 95% CI 1.02 to 4.94; 1 study, 20 participants, very low-quality evidence). Results did not support using any specific pharmacological approach for the management of opium withdrawal due to generally very low-quality evidence and small or no differences between treatments. However, it seems that opium withdrawal symptoms are significant, especially at days 2 to 4 after discontinuation of opium. All of the assessed medications might be useful in alleviating symptoms. Those who receive clonidine might experience hypotension.

Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial.

PubMed

Dunn, Kelly E; Tompkins, D Andrew; Bigelow, George E; Strain, Eric C

2017-09-01

Opioid use disorder (OUD) is a significant public health problem. Supervised withdrawal (ie, detoxification) from opioids using clonidine or buprenorphine hydrochloride is a widely used treatment. To evaluate whether tramadol hydrochloride extended-release (ER), an approved analgesic with opioid and nonopioid mechanisms of action and low abuse potential, is effective for use in supervised withdrawal settings. A randomized clinical trial was conducted in a residential research setting with 103 participants with OUD. Participants' treatment was stabilized with morphine, 30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine (n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted, and patients were crossed-over to double-blind placebo during a post-taper period. The study was conducted from October 25, 2010, to June 23, 2015. Retention, withdrawal symptom management, concomitant medication utilization, and naltrexone induction. Results were analyzed over time and using area under the curve for the intention-to-treat and completer groups. Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white; mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were significantly more likely to be retained at the end of the taper compared with clonidine participants (22 [61.1%]); tramadol ER retention was intermediate and did not differ significantly from that of the other groups (26 [72.2%]; χ2 = 8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score (taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F2,170 = 3.6, P = .03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE, .40]; post-taper mean, 4.14 [SE, .30]; F2,170 = 15.7, P < .001), but no group effects or group × phase interactions. Analyses of area under the curve of SOWS total scores showed significant reductions (F2,159 = 17.7, P < .001) in withdrawal severity between the taper and post-taper periods for clonidine (taper mean, 13.1; post-taper mean, 3.2; P < .001) and tramadol ER (taper mean, 7.4; post-taper mean, 2.8; P = .03), but not buprenorphine (taper mean, 6.4; post-taper mean, 7.4). Use of concomitant medication increased significantly (F2,159 = 30.7,  P < .001) from stabilization to taper in the clonidine (stabilization mean, 0.64 [SE, .05]; taper mean, 1.54 [SE, .10]; P < .001) and tramadol ER (stabilization mean, 0.53 [SE, .05]; taper mean, 1.19 [SE, .09]; P = .003) groups and from stabilization to post taper in the buprenorphine group (stabilization mean, 0.46 [SE, .05] post-taper mean, 1.17 [SE, .09]; P = .006), suggesting higher withdrawal for those groups during those periods. Naltrexone initiation was voluntary and the percentage of participants choosing naltrexone therapy within the clonidine (8 [22.2%]), tramadol ER (7 [19.4%]), or buprenorphine (3 [9.7%]) groups did not differ significantly (χ2 = 2.5, P = .29). The results of this trial suggest that tramadol ER is more effective than clonidine and comparable to buprenorphine in reducing opioid withdrawal symptoms during a residential tapering program. Data support further examination of tramadol ER as a method to manage opioid withdrawal symptoms. Clinicaltrials.gov Identifier: NCT01188421.

Preliminary effects of progressive muscle relaxation on cigarette craving and withdrawal symptoms in experienced smokers in acute cigarette abstinence: a randomized controlled trial.

PubMed

Limsanon, Thatsanee; Kalayasiri, Rasmon

2015-03-01

Cigarette craving usually occurs in conjunction with unpleasant feelings, including stress, as part of a withdrawal syndrome. Progressive muscle relaxation (PMR), a behavioral technique used to reduce stress by concentrating on achieving muscle relaxation, may reduce levels of cigarette craving and other substance-related negative feelings and withdrawal symptoms. Demographic and cigarette use data were collected from 32 experienced smokers at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand using the Semi-Structured Assessment for Drug Dependence and Alcoholism. Participants were asked to refrain from smoking for at least 3 hours before the visit (acute abstinence) and were randomly allocated to a 1-session PMR group (n =16) or a control activity group (e.g., reading newspaper, n =16). The intervention group was instructed to practice PMR individually in a quiet, private, air-conditioned room for about 20minutes. Craving, other substance-related feelings, and autonomic nervous responses (e.g., blood pressure and pulse rate) were assessed immediately before and after the 1-session intervention. There were no differences in demographics, cigarette use/dependence, and baseline craving characteristics between the PMR and control groups. However, the control group had higher levels of high and paranoia feeling, and pulse rate than the PMR group at baseline. After practicing PMR, but not after a control activity, smokers undergoing acute abstinence had significantly lower levels of cigarette craving, withdrawal symptoms, and systolic blood pressure than at baseline. After controlling for baseline differences, abstaining smokers using PMR had lower levels of cigarette craving, withdrawal symptoms, and systolic blood pressure than smokers who undertook a control activity. PMR significantly reduces cigarette craving, withdrawal symptoms, and blood pressure in smokers undergoing acute abstinence. PMR may be used as an adjunct to cigarette dependency treatments. Copyright © 2014. Published by Elsevier Ltd.

Development of Thermally Stable and Highly Fluorescent IR Dyes

NASA Technical Reports Server (NTRS)

Bu, Xiu R.

2004-01-01

Fluorophores are the core component in various optical applications such as sensors and probes. Fluorphores with low-energy or long wavelength emission, in particular, in NIR region, possess advantages of low interference and high sensitivity. In this study, we has explored several classes of imidazole-based compounds for NIR fluorescent properties and concluded: (1) thiazole-based imidazole compounds are fluorescent; (2) emission energy is tunable by additional donor groups; (3) they also possess impressive two- photon absorption properties; and (4) fluorescence emission can be induced by two- photon input. This report summarizes (1) synthesis of new series of fluorophore; (2) impact of electron-withdrawing groups on fluorescent property; (3) unique property of two-photon absorption; and (4) on-going development.

Engineering of Porphyrin Molecules for Use as Effective Cathode Interfacial Modifiers in Organic Solar Cells of Enhanced Efficiency and Stability.

PubMed

Tountas, Marinos; Verykios, Apostolis; Polydorou, Ermioni; Kaltzoglou, Andreas; Soultati, Anastasia; Balis, Nikolaos; Angaridis, Panagiotis A; Papadakis, Michael; Nikolaou, Vasilis; Auras, Florian; Palilis, Leonidas C; Tsikritzis, Dimitris; Evangelou, Evangelos K; Gardelis, Spyros; Koutsoureli, Matroni; Papaioannou, George; Petsalakis, Ioannis D; Kennou, Stella; Davazoglou, Dimitris; Argitis, Panagiotis; Falaras, Polycarpos; Coutsolelos, Athanassios G; Vasilopoulou, Maria

2018-06-20

In the present work, we effectively modify the TiO 2 electron transport layer of organic solar cells with an inverted architecture using appropriately engineered porphyrin molecules. The results show that the optimized porphyrin modifier bearing two carboxylic acids as the anchoring groups and a triazine electron-withdrawing spacer significantly reduces the work function of TiO 2 , thereby reducing the electron extraction barrier. Moreover, the lower surface energy of the porphyrin-modified substrate results in better physical compatibility between the latter and the photoactive blend. Upon employing porphyrin-modified TiO 2 electron transport layers in PTB7:PC 71 BM-based organic solar cells we obtained an improved average power conversion efficiency up to 8.73%. Importantly, porphyrin modification significantly increased the lifetime of the devices, which retained 80% of their initial efficiency after 500 h of storage in the dark. Because of its simplicity and efficacy, this approach should give tantalizing glimpses and generate an impact into the potential of porphyrins to facilitate electron transfer in organic solar cells and related devices.

Sleep, Internalizing Problems, and Social Withdrawal: Unique Associations in Clinic-Referred Youth With Elevated Sluggish Cognitive Tempo Symptoms.

PubMed

Rondon, Ana T; Hilton, Dane C; Jarrett, Matthew A; Ollendick, Thomas H

2018-02-01

We compared clinic-referred youth with ADHD + sluggish cognitive tempo (SCT; n = 34), ADHD Only ( n = 108), and SCT Only ( n = 22) on demographics, co-occurring symptomatology, comorbid diagnoses, and social functioning. In total, 164 youth (age = 6-17 years, M = 9.97) and their parent(s) presented to an outpatient clinic for a psychoeducational assessment. Between-group analyses and regressions were used to examine study variables. SCT groups were older and exhibited more parent-reported internalizing problems, externalizing problems, sleep problems, and social withdrawal on the Child Behavior Checklist. No significant differences emerged between groups on the Teacher Report Form. Regression analyses involving multiple covariates revealed that SCT symptoms were uniquely related to social withdrawal but not general social problems. Based on parent report, SCT symptoms have a unique relationship with internalizing problems, sleep problems, and social withdrawal. Future research should explore correlates of SCT in youth using multiple informants.

Comparison of conventional L-thyroxine withdrawal and moderate hypothyroidism in preparation for whole-body 131-I scan and thyroglobulin testing.

PubMed

Marturano, I; Russo, M; Spadaro, A; Latina, A; Malandrino, P; Regalbuto, C

2015-09-01

After thyroidectomy for thyroid cancer, patients often withdraw L-T4 for diagnostic or therapeutic purposes, showing signs and symptoms of hypothyroidism. A slighter hypothyroidism (reducing L-T4 to one-half) has been proposed to limit these inconveniences. We evaluated half-dose L-T4 protocol, in comparison to conventional L-T4 withdrawal, in terms of effectiveness and improvement of clinical and biochemical disorders. We randomized 55 thyroid cancer patients into two groups: 29 patients underwent 5 weeks of half-dose of previous L-T4 treatment (HD group); 26 patients replaced L-T4 with L-T3 for 3 weeks followed by 2 weeks of withdrawal (TW group). Clinical features (Zulewsky clinical score) and biochemical parameters (lipids, liver, and muscle enzymes) were evaluated in all patients at baseline and after 5 weeks. Total cholesterol, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase increased at 5 weeks in both groups, but significantly more in TW, but no difference was found by clinical score. Patients who achieved the thyroid-stimulating hormone (TSH) target value (25 µU/ml) were 92.3% in TW group and 48.3% in HD group (p < 0.001). In the HD group, only basal TSH statistically correlated with the achievement of the TSH target. Receiver operating characteristic curves indicated that a basal TSH ≥0.52 μU/ml is required to reach an adequate TSH level. Half-dose L-T4 protocol, compared to conventional L-T4 withdrawal, is associated with less biochemical disorders but no significant clinical advantage. Therefore, the half-dose protocol reaches an adequate TSH target in 48.3% of patients and is not effective unless basal serum TSH is ≥0.52 μU/ml.

Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading.

PubMed

Garcia-Alcala, Hector; Santos Vichido, Celia Isabel; Islas Macedo, Silverio; Genestier-Tamborero, Christelle Nathalie; Minutti-Palacios, Marissa; Hirales Tamez, Omara; García, Carlos; Ziegler, Dan

2015-01-01

Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA) over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid) for 4 weeks (phase 1). Subsequently, responders were randomized to receive ALA (600 mg qd; n = 16) or to ALA withdrawal (n = 17) for 16 weeks (phase 2). During phase 1, the Total Symptom Score (TSS) decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p < 0.05) and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p < 0.05). In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid) administration of ALA, subsequent treatment with ALA (600 mg qd) over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879.

Mechanistic aspects of hydrogen abstraction for phenolic antioxidants. Electronic structure and topological electron density analysis.

PubMed

Singh, Nakul; O'Malley, Patrick J; Popelier, Paul L A

2005-02-21

Density functional calculations using the B3LYP functional are used to provide insight into the hydrogen abstraction mechanism of phenolic antioxidants. The energy profiles for 13 ortho, meta, para and di-methyl substituted phenols with hydroperoxyl radical have been determined. An excellent correlation between the enthalpy (DeltaH) and activation energy (DeltaEa) was found, obeying the Evans-Polanyi rule. The effects of hydrogen bonding on DeltaEa are also discussed. Electron donating groups at the ortho and para positions are able to lower the activation energy for hydrogen abstraction. The highly electron withdrawing fluoro substituent increases the activation energies relative to phenol at the meta position but not at the para position. The electron density is studied using the atoms in molecules (AIM) approach. Atomic and bond properties are extracted to describe the hydrogen atom abstraction mechanism. It is found that on going from reactants to transition state, the hydrogen atom experiences a loss in volume, electronic population and dipole moment. These features suggest that the phenol hydroperoxyl reactions proceed according to a proton coupled electron transfer (PCET) as opposed to a hydrogen atom transfer (HAT) mechanism.

The association between social anhedonia, withdrawal and psychotic experiences in general and high-risk populations.

PubMed

Velthorst, Eva; Meijer, Carin

2012-07-01

Social anhedonia (SA) and withdrawal are clinically relevant phenomena in schizophrenia. To examine the nature of the overlap between SA, withdrawal and positive symptoms, we investigated whether the co-occurrence of these phenotypes is more prominent in siblings of patients with a psychotic disorder compared to healthy controls, and if this association is independent of the amount of distress caused by psychotic experiences (PEs). Data were derived from 646 unaffected siblings and 326 healthy controls who were included in the Dutch Genetic Risk and Outcome in Psychosis (GROUP) study. PEs were assessed with the Community Assessment of Psychic Experiences and the Structured Interview for Schizotypy-Revised was used to examine social anhedonia and withdrawal. Our results show relatively small but significant cross-sectional associations between SA, withdrawal and PEs in unaffected siblings and none in the control group, irrespective of the level of distress caused by PEs. The findings of the present study suggest that the overlap between SA, withdrawal and psychotic symptoms often reported in schizophrenia patients, may at least partly reflect a shared genetic vulnerability, instead of merely being either a state marker of - or reaction to - acute psychotic symptoms. Copyright © 2012. Published by Elsevier B.V.

Substituent Effects in the Benzene Dimer are Due to Direct Interactions of the Substituents with the Unsubstituted Benzene

PubMed Central

Wheeler, Steven E.; Houk, K. N.

2009-01-01

The prevailing views of substituent effects in the sandwich configuration of the benzene dimer are flawed. For example, in the polar/π model of Cozzi and co-workers (J. Am. Chem. Soc. 1992, 114, 5729), electron-withdrawing substituents enhance binding in the benzene dimer by withdrawing electron density from the π-cloud of the substituted ring, reducing the repulsive electrostatic interaction with the non-substituted benzene. Conversely, electron-donating substituents donate excess electrons into the π-system and diminish the π-stacking interaction. We present computed interaction energies for the sandwich configuration of the benzene dimer and 24 substituted dimers, as well as sandwich complexes of substituted benzenes with perfluorobenzene. While the computed interaction energies correlate well with σm values for the substituents, interaction energies for related model systems demonstrate that this trend is independent of the substituted ring. Instead, the observed trends are consistent with direct electrostatic and dispersive interactions of the substituents with the unsubstituted ring. PMID:18652453

Caffeine Withdrawal and Dependence: A Convenience Survey Among Addiction Professionals.

PubMed

Budney, Alan J; Brown, Pamela C; Griffiths, Roland R; Hughes, John R; Juliano, Laura M

2013-06-01

Caffeine withdrawal was included in the research appendix of the DSM-IV to encourage additional research to assist with determining its status for the next version of the manual. Caffeine dependence was not included because of a lack of empirical research at the time of publication. This study assessed the beliefs of addiction professionals about the clinical importance of caffeine withdrawal and dependence. A 6-item survey was developed and delivered electronically to the members of six professional organizations that focus on addiction. Open-ended comments were also solicited. Five hundred members responded. The majority (95%) thought that cessation of caffeine could produce a withdrawal syndrome, and that caffeine withdrawal can have clinical importance (73%); however, only half (48%) thought that caffeine withdrawal should be included in the Diagnostic and Statistical Manual of Mental Disorders (DSM). A majority (58%) believed that some people develop caffeine dependence; however, only 44% indicated that it should be in the DSM. Comments suggested that trepidation about inclusion of caffeine diagnoses was due to the concerns about the field of psychiatry being criticized for including common disorders with a relatively low clinical severity. Others, however, expressed an urgent need to take caffeine-related problems more seriously. The majority of addiction professionals believe that caffeine withdrawal and dependence disorders exist and are clinically important; however, these professionals are divided in whether caffeine withdrawal and dependence should be included in DSM. Wider dissemination of the extant literature on caffeine withdrawal and additional research on caffeine dependence will be needed to provide additional guidance to policymakers and healthcare workers.

Improvement in Titanium Complexes Bearing Schiff Base Ligands in the Ring-Opening Polymerization of L-Lactide: A Dinuclear System with Hydrazine-Bridging Schiff Base Ligands.

PubMed

Tseng, Hsi-Ching; Chen, Hsing-Yin; Huang, Yen-Tzu; Lu, Wei-Yi; Chang, Yu-Lun; Chiang, Michael Y; Lai, Yi-Chun; Chen, Hsuan-Ying

2016-02-15

A series of titanium (Ti) complexes bearing hydrazine-bridging Schiff base ligands were synthesized and investigated as catalysts for the ring-opening polymerization (ROP) of L-lactide (LA). Complexes with electron withdrawing or steric bulky groups reduced the catalytic activity. In addition, the steric bulky substituent on the imine groups reduced the space around the Ti atom and then reduced LA coordination with Ti atom, thereby reducing catalytic activity. All the dinuclear Ti complexes exhibited higher catalytic activity (approximately 10-60-fold) than mononuclear L(Cl-H)-TiOPr2 did. The strategy of bridging dinuclear Ti complexes with isopropoxide groups in the ROP of LA was successful, and adjusting the crowded heptacoordinated transition state by the bridging isopropoxide groups may be the key to our successful strategy.

Theoretical Study of Electron Transfer Properties of Squaraine Dyes for Dye Sensitized Solar Cell

NASA Astrophysics Data System (ADS)

Juwita, Ratna; Tsai, Hui-Hsu Gavin

2018-01-01

The environmental issues and high cost of Ru create many scientists to explore cheaper and safer sensitizer as alternative for dye sensitized solar cells (DSCs). Dyes play an important role in solar energy conversion efficiency. The squaraine (SQ) dyes has good spectral match with the solar spectra, therefore, SQ dyes have great potential for the applications in DSCs. SQ01_CA is an unsymmetrical SQ dye, reported by Grätzel and colleagues in 2007, featuring a D-π-spacer-A framework and has a carboxylic acid anchoring group. The electron donating ability of indolium in SQ01_CA and SQ01_CAA dyes is relatively weak, better performance may be achieved by introducing an additional donor moiety into indolium [1]. In this study, we investigate six unsymmetrical SQ dyes adsorbed on a (TiO2)38 cluster [2] using density functional theory (DFT) and time-dependent DFT to study electron transfer properties of squaraine dyes on their photophysical. SQ01_CA, WH-SQ01_CA, and WH-SQ02_CA use a carboxylic acid group as its electron acceptor. Furthermore, SQ01_CAA, WH-SQ01_CAA, and WH-SQ02_CAA use a cyanoacrylic acid group as its electron acceptor. WH-SQ01_CA and WH-SQ01_CAA have an alkyl, while WH-SQ02_CA and WH-SQ02_CAA have alkoxyl substituted diarylamines to the indolium donor of sensitizer SQ01_CA. Our calculations show with additional diarylamines in donor tail of WH-SQ02_CAA, the SQ dyes have red-shifted absorption and have slightly larger probability of electron density transferred to TiO2 moiety. Furthermore, an additional -CN group as electron a withdrawing group in the acceptor exhibits red-shifted absorption and enhances the electron density transferred to TiO2 and anchoring moiety after photo-excitation. The tendency of calculated probabilities of electron density being delocalized into TiO2 and driving force for excited-state electron injection of these studied SQ dyes is compatible with their experimentally observed.

Aloe vera Aqueous Extract Effect on Morphine Withdrawal Syndrome in Morphine-Dependent Female Rats.

PubMed

Shahraki, Mohammad Reza; Mirshekari, Hamideh; Sabri, Azame

2014-09-01

Aloe vera is a medicinal herb used as an anti-inflammatory and sedative agent. The current study aimed to evaluate the effect of Aloe vera aqueous extract on morphine withdrawal symptoms in morphine-dependent female rats. The current research was performed on 40 female Wista-Albino rats which were made dependent on morphine using Houshyar protocol and were randomly divided into five groups (A, B, C, D, and E). Group A did not receive any agent in the period of handling but other groups (B, C, D and E) received 5, 10, 20 and 40 mg/kg of Aloe vera aqueous extract by gavage, three times daily for a week, respectively. Withdrawal symptoms, stool form, agitation, disparity, floppy eyelids, and body mass variations were checked for 10 days. The obtained data were analyzed using SPSS v.11 software, and Friedman, Kruskal-Wallis, and Mann-Whitney statistical tests. Statistical difference was considered significant (P < 0.05). The results of the present study showed that agitation, disparity, and floppy eyelids in group E were significantly higher than those of others groups; however, these symptoms in group C were significantly lower than those of the other groups. The results of the present study revealed that the Aloe vera aqueous extract had various effects on morphine withdrawal syndrome in morphine-dependent female rats .

Aloe vera Aqueous Extract Effect on Morphine Withdrawal Syndrome in Morphine-Dependent Female Rats

PubMed Central

Shahraki, Mohammad Reza; Mirshekari, Hamideh; Sabri, Azame

2014-01-01

Background: Aloe vera is a medicinal herb used as an anti-inflammatory and sedative agent. Objectives: The current study aimed to evaluate the effect of Aloe vera aqueous extract on morphine withdrawal symptoms in morphine-dependent female rats. Patients and Methods: The current research was performed on 40 female Wista-Albino rats which were made dependent on morphine using Houshyar protocol and were randomly divided into five groups (A, B, C, D, and E). Group A did not receive any agent in the period of handling but other groups (B, C, D and E) received 5, 10, 20 and 40 mg/kg of Aloe vera aqueous extract by gavage, three times daily for a week, respectively. Withdrawal symptoms, stool form, agitation, disparity, floppy eyelids, and body mass variations were checked for 10 days. The obtained data were analyzed using SPSS v.11 software, and Friedman, Kruskal-Wallis, and Mann-Whitney statistical tests. Statistical difference was considered significant (P < 0.05). Results: The results of the present study showed that agitation, disparity, and floppy eyelids in group E were significantly higher than those of others groups; however, these symptoms in group C were significantly lower than those of the other groups. Conclusions: The results of the present study revealed that the Aloe vera aqueous extract had various effects on morphine withdrawal syndrome in morphine-dependent female rats . PMID:25593890

Shy, but funny? Examining peer-valued characteristics as moderators of the associations between anxious-withdrawal and peer outcomes during early adolescence.

PubMed

Markovic, Andrea; Bowker, Julie C

2015-04-01

Research has revealed significant heterogeneity in the group-level peer outcomes associated with anxious-withdrawal, but little is known about possible sources of this heterogeneity during early adolescence. This study of 271 young adolescents (49 % female; M age = 11.54 years) examined whether the concurrent and short-term longitudinal (3 month period) associations between peer-nominated anxious-withdrawn behaviors and three group-level peer outcomes (overt victimization, peer acceptance, popularity) varied as a function of peer-valued characteristics (humor, prosocial behavior, physical attractiveness, athletic ability) and gender, after accounting for the effects of involvement in mutual friendships. Regression analyses revealed that the associations between anxious-withdrawal and peer outcomes were moderated by peer-valued characteristics and, in many cases, gender. For example, anxious-withdrawal was related positively to overt victimization for all adolescents who were high in prosocial behavior. But, anxious-withdrawal was related negatively to popularity for adolescent boys who were high in prosocial behavior and adolescent girls who were low in prosocial behavior. Anxious-withdrawal also predicted increases in acceptance for adolescent girls who were high in humor, but decreases in acceptance for adolescent boys who were high in humor. Several additional moderator effects were found for boys only. The findings highlight the importance of considering the unique constellation of characteristics displayed by anxious-withdrawn young adolescents in studies on peer experiences at the group-level of social complexity.

Elevated levels of endothelial cell-derived microparticles following short-term withdrawal of continuous positive airway pressure in patients with obstructive sleep apnea: data from a randomized controlled trial.

PubMed

Ayers, Lisa; Stoewhas, Anne-Christin; Ferry, Berne; Stradling, John; Kohler, Malcolm

2013-01-01

Obstructive sleep apnea has been associated with impaired endothelial function; however, the mechanisms underlying this association are not completely understood. Cell-derived microparticles may provide a link between obstructive sleep apnea and endothelial dysfunction. This randomized controlled trial aimed to examine the effect of a 2-week withdrawal of continuous positive airway pressure (CPAP) therapy on levels of circulating microparticles. Forty-one obstructive sleep apnea patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continuing therapeutic CPAP, for 2 weeks. Polysomnography was performed and circulating levels of microparticles were analyzed by flow cytometry at baseline and 2 weeks. CPAP withdrawal led to a recurrence of obstructive sleep apnea. Levels of CD62E+ endothelium-derived microparticles increased significantly in the CPAP withdrawal group compared to the continuing therapeutic CPAP group (median difference in change +32.4 per µl; 95% CI +7.3 to +64.1 per µl, p = 0.010). CPAP withdrawal was not associated with a statistically significant increase in granulocyte, leukocyte, and platelet-derived microparticles when compared with therapeutic CPAP. Short-term withdrawal of CPAP therapy leads to a significant increase in endothelium-derived microparticles, suggesting that microparticle formation may be causally linked to obstructive sleep apnea and may promote endothelial activation. Copyright © 2012 S. Karger AG, Basel.

Tobacco withdrawal among opioid-dependent smokers.

PubMed

Streck, Joanna M; Heil, Sarah H; Higgins, Stephen T; Bunn, Janice Y; Sigmon, Stacey C

2018-04-01

Prevalence of cigarette smoking among opioid-dependent individuals is 6-fold that of the general U.S. adult population and their quit rates are notoriously poor. One possible reason for the modest cessation outcomes in opioid-dependent smokers may be that they experience more severe tobacco withdrawal upon quitting. In this secondary analysis, we evaluated tobacco withdrawal in opioid-dependent (OD) smokers versus smokers without co-occurring substance use disorders (SUDs). Participants were 47 methadone- or buprenorphine-maintained smokers and 25 non-SUD smokers who completed 1 of several 2-week studies involving daily visits for biochemical monitoring, delivery of financial incentives contingent on smoking abstinence, and assessment of withdrawal via the Minnesota Nicotine Withdrawal Scale (MNWS). Prior to quitting smoking, OD smokers presented with higher baseline withdrawal scores than non-SUD smokers (1.7 ± 0.2 vs. 0.7 ± 0.2, respectively; F [1, 63] = 7.31, p < .001). Withdrawal scores in both groups decreased over the subsequent 2-week period with no group differences, F (1, 910) = 0.50, p = .48. A similar pattern was observed on craving (i.e., Desire to Smoke item of MNWS), although the trajectory of decrease over time on this item was also moderated by gender. Overall, there was no difference in withdrawal during biochemically verified smoking abstinence between OD and non-SUD smokers, suggesting that elevated withdrawal severity following quitting may not be a major factor contributing to the poor cessation outcomes consistently observed among OD smokers. Further scientific efforts are needed to improve our understanding of the high smoking rates and modest cessation outcomes in this challenging population. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Variations in the neonatal environment modulate adult behavioral and brain responses to palatable food withdrawal in adult female rats.

PubMed

Colman, Juliana Barcellos; Laureano, Daniela Pereira; Reis, Tatiane Madeira; Krolow, Rachel; Dalmaz, Carla; Benetti, Carla da Silva; Silveira, Patrícia Pelufo

2015-02-01

Early handling alters adult behavioral responses to palatable food and to its withdrawal following a period of chronic exposure. However, the central mechanisms involved in this phenomenon are not known. Since neonatal handling has persistent effects on stress and anxiety responses, we hypothesized that its involvement in the aforementioned association may be associated with differential neuroadaptations in the amygdala during withdrawal periods. Litters were randomized into two groups: handled (H, removed from their dam for 10min per day from the first to the tenth postnatal day and placed in an incubator at 32°C) and non-handled (NH). Experiment 1: on PNDs 80-100, females were assigned to receive palatable food+rat chow for 15 or 30 days, and these two groups were compared in terms of palatable food preference, body weight and abdominal fat deposition. In Experiment 2, H and NH rats were exposed to a chronic diet of palatable food+rat chow for 15 days, followed by (a) no withdrawal, (b) 24h withdrawal from palatable food (receiving only rat chow) or (c) 7-day withdrawal from palatable food (receiving only rat chow). Body weight, 10-min rebound palatable food intake, abdominal fat deposition, serum corticosterone as well as TH and pCREB levels in the amygdala were then compared between groups. Experiment 1-chronic exposure to palatable food induces comparable metabolic effects after 15 and 30 days. Experiment 2-neonatal handling is associated with a peculiar response to palatable food withdrawal following chronic exposure for 15 days. Rats exposed to early handling ingested less of this food after a 24h withdrawal period, and displayed increased amygdala TH and pCREB levels. Variations in the neonatal environment affect both behavioral responses and amygdala neuroadaptation to acute withdrawal from a palatable diet. These findings contribute to the comprehension of the mechanisms that link early life events and altered feeding behavior and related morbidities such as obesity in adulthood. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

A placebo-controlled trial of mirtazapine for the management of methamphetamine withdrawal.

PubMed

Cruickshank, Christopher C; Montebello, Mark E; Dyer, Kyle R; Quigley, Allan; Blaszczyk, Jozef; Tomkins, Sally; Shand, Diana

2008-05-01

As an antidepressant with sedative and anxiolytic properties, mirtazapine may be an appropriate pharmacotherapy for methamphetamine withdrawal. This study sought to examine whether mirtazapine improves retention and alleviates methamphetamine withdrawal symptoms in an out-patient setting. An out-patient double-blind, randomised placebo-controlled trial of mirtazapine for the treatment of methamphetamine withdrawal was conducted (15 mg nocte for 2 days, 30 mg nocte for 12 days). Both groups were offered narrative therapy counselling. Measures recorded on days 0, 3, 7, 14 and 35 included: treatment retention, Amphetamine Cessation Symptoms Assessment, the Athens Insomnia Scale, the Brief Symptom Inventory, the Depression-Anxiety-Stress Scale (DASS), Severity of Dependence scale and the Opiate Treatment Index Drug Use subscale. Thirty-one participants were recruited (18 placebo, 13 mirtazapine) and 52% completed the 2-week medication phase. No significant differences between the mirtazapine and placebo groups in retention, or any symptom measure were observed, except greater DASS-anxiety and longer sleep duration were measured at baseline among the mirtazapine group. Results suggest that mirtazapine does not facilitate retention or recruitment in out-patient methamphetamine withdrawal treatment, although recruitment may have been insufficient to identify a significant treatment effect. The potential role of narrative therapy for methamphetamine dependent patients deserves further exploration.

Blood and tissue fatty acid compositions, lipoprotein levels, performance and meat flavor of broilers fed fish oil: changes in the pre- and post-withdrawal design.

PubMed

Aghaei, N; Safamehr, A; Mehmannavaz, Y; Chekaniazar, S

2012-12-01

Administration of fish oil (FO) in broiler diets can elevate α-linolenic acid (ALA), eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) levels, which are protective against cardiovascular disease. However, optimization based solely on n-3 polyunsaturated fatty acid (n-3 PUFA) enrichment in chicken meat could lead to lower meat quality, unless the withdrawal period (plan) is applied for 1 week. The present study investigated whether the incorporation of FO in the diet for 32 days followed by its withdrawal for 1 week affected blood lipid profiles, lipoprotein particles, performance and meat flavor in male broiler chickens. Two hundred and forty birds (1-day-old, Ross 308) were assigned to 1 of 4 dietary groups: 0%, 1%, 2% or 3% FO with four replicates. Broilers were fed for 49 days according to a 4-phase feeding program. The experimental phase comprised day 11 to 42, and FO was removed on day 42. Blood samples were collected during the pre- and post-withdrawal period after the recordings before slaughter. The FO groups demonstrated decreased low-density lipoprotein (LDL) and increased high-density lipoprotein levels on day 42 (P < 0.01); however, these values were not significant after design withdrawal. Diet supplementation with FO elevated the blood levels of palmitic acid (C16:0) and n-3 PUFAs, especially long-chain (LC) PUFAs (EPA, C20:5n-3 and DHA, C22:6n-3), and caused a decline in the level of arachidonic acid (AA, C20:4n-6; P < 0.05). Application of a one-week withdrawal period resulted in a decrease in (P < 0.05) linoleic acid (C18:2n-6) and an increase in the level of AA, unlike their amounts on day 42. Although blood and tissue LC n-3 PUFA levels on day 49 were significantly higher in the FO groups compared with the control, they demonstrated a substantial decrease on day 49 compared with day 42. The best results, mainly the lowest n-6/n-3 fatty acids (FAs) and feed conversion ratio (FCRs), were observed for 3% FO (group T4), even after institution of the withdrawal design. Degradation of total n-3 FAs deposited in tissues occurred after instituting the withdrawal plan diet, but deposited levels of EPA and DHA in tissues could ensure omega-3 enrichment of broiler meat in groups 3 and 4. On the basis of the dissatisfaction of the panelists toward group 4 meats (scored as near to acceptable) and their satisfaction with cooked samples of T3 (scored as good), group 3 meats were selected as good-quality n-3-enriched broiler meat.

Changes in Expression of Dopamine, Its Receptor, and Transporter in Nucleus Accumbens of Heroin-Addicted Rats with Brain-Derived Neurotrophic Factor (BDNF) Overexpression.

PubMed

Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Liang, Wenmei

2017-06-09

BACKGROUND The aim of this study was to explore how changes in the expression of BDNF in MLDS change the effect of BDNF on dopamine (DA) neurons, which may have therapeutic implications for heroin addiction. MATERIAL AND METHODS We established a rat model of heroin addiction and observed changes in the expression of BDNF, DA, dopamine receptor (DRD), dopamine transporter (DAT), and other relevant pathways in NAc. We also assessed the effect of BDNF overexpression in the NAc, behavioral changes of heroin-conditioned place preference (CPP), and naloxone withdrawal in rats with high levels of BDNF. We established 5 adult male rat groups: heroin addiction, lentivirus transfection, blank virus, sham operation, and control. The PCR gene chip was used to study gene expression changes. BDNF lentivirus transfection was used for BDNF overexpression. A heroin CPP model and a naloxone withdrawal model of rats were established. RESULTS Expression changes were found in 20 of the 84 DA-associated genes in the NAc of heroin-addicted rats. Weight loss and withdrawal symptoms in the lentivirus group for naloxone withdrawal was less than in the blank virus and the sham operation group. These 2 latter groups also showed significant behavioral changes, but such changes were not observed in the BDNF lentivirus group before or after training. DRD3 and DAT increased in the NAc of the lentivirus group. CONCLUSIONS BDNF and DA in the NAc are involved in heroin addiction. BDNF overexpression in NAc reduces withdrawal symptoms and craving behavior for medicine induced by environmental cues for heroin-addicted rats. BDNF participates in the regulation of the dopamine system by acting on DRD3 and DAT.

Effect of forced exercise and exercise withdrawal on memory, serum and hippocampal corticosterone levels in rats.

PubMed

Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

2015-10-01

Evidence suggests that there are positive effects of exercise on learning and memory. Moreover, some studies have demonstrated that forced exercise plays the role of a stressor. This study was aimed at investigating the effects of different timing of exercise and exercise withdrawal on memory, and serum and hippocampal corticosterone (CORT) levels. Wistar rats were randomly divided into five groups: control, sham, exercise-rest (exercise withdrawal), rest-exercise (exercised group), and exercise-exercise (continuous exercise). Rats were forced to run on a treadmill for 1 h/day at a speed 20-21-m/min. Memory function was evaluated by the passive avoidance test in different intervals (1, 7 and 21 days) after foot shock. Findings showed that after the exercise withdrawal, short-term and mid-term memories, had significant enhancement compared to the control group, while the long-term memory did not present this result. In addition, the serum and hippocampal CORT levels were at the basal levels after the rest period in the exercise-rest group. In the rest-exercise group, exercise improved mid- and long-term memories, whereas continuous exercise improved all types short-, mid- and long-term memories, particularly the mid-term memory. Twenty-one and forty-two days of exercise significantly decreased the serum and hippocampal CORT levels. It seems that exercise for at least 21 days with no rest could affect biochemical factors in the brain. Also, regular continuous exercise plays an important role in memory function. Hence, the duration and withdraw of exercise are important factors for the neurobiological aspects of the memory responses.

Workplace relational factors and physicians' intention to withdraw from practice.

PubMed

Masselink, Leah E; Lee, Shoou-Yih D; Konrad, Thomas R

2008-01-01

Physician turnover threatens continuity of care for patients and is a huge expense for health care organizations. Health care organizations have been advised to help physicians build positive relations with colleagues, staff, and patients as a strategy to socially integrate physicians in the workplace and to increase physician retention. Although these recommendations are touted as "evidence-based" practices, the importance of workplace relationships for physician retention has not been established empirically. The purpose of this study is to examine two questions: Are physicians who report better relationships with colleagues, staff, and patients less likely to intend to withdraw from practice? Do the effects of these relational factors differ for large-group and solo/small-group practice physicians? Using data from the Physician Worklife Survey, we analyzed the associations between physicians' reported relationships with colleagues, staff, and patients and intention to withdraw from practice within 2 years using logistic regression. : Relationships with colleagues had a significant and negative association with intended withdrawal from practice for large-group practice physicians. The joint effect of relationships with colleagues, staff, and patients was significant for large-group practice physicians, but it only approached significance for solo/small-group practice physicians. This study suggests that workplace relationships may influence physicians' intention to withdraw from practice, but the mechanisms by which they do so are unclear. Possible interventions to improve physician retention include promotion of informal mentoring and efforts to support community involvement of physicians and their families. Further research examining the role of these and other programs in promoting physician retention can help employers to foster positive workplace relationships and improve retention.

The effects of nicotine self-administration and withdrawal on concurrently available chow and sucrose intake in adult male rats.

PubMed

Bunney, Patricia E; Burroughs, Danielle; Hernandez, Christine; LeSage, Mark G

2016-02-01

Carbohydrate intake, preference, and taste thresholds may be altered in current and former cigarette smokers, which may mediate weight gain and risk for obesity in individuals who quit smoking. Attempts to model these effects in rodents have primarily used noncontingent nicotine administration. The purpose of this research was to characterize changes in chow and sucrose intake in rats during a 23-h access model of i.v. nicotine self-administration (NSA), in which rats lever-pressed for chow, sucrose, and nicotine under concurrent fixed-ratio (FR) 1 schedules. Male rats were assigned to one of three groups that differed in food and drug availability. The Nicotine C+S group had concurrent access to nicotine, chow, and sucrose. The Saline C+S group had access to saline, chow, and sucrose. The Nicotine C-Only group had access to nicotine and chow, but not sucrose. Changes in food intake and weight gain were assessed during baseline, NSA, and nicotine withdrawal (i.e., saline extinction). Weight gain was significantly slowed during NSA and increased during withdrawal, but did not differ between the nicotine groups. NSA produced a significant decrease in both chow and sucrose intake. Gradual tolerance to nicotine's effects on sucrose, but not chow intake, occurred. During withdrawal, chow and sucrose intake increased, with a larger percent increase in sucrose intake compared to chow. The proportion of total food intake from sucrose was greater at the end of withdrawal compared to baseline, indicating a history of nicotine intake changed dietary preference. Combined, these results indicate that sucrose intake is more resistant to nicotine's appetite suppressant effects and withdrawal from nicotine produces a greater increase in sweet food intake alongside general increases in chow intake. Changes in overall food intake in current and ex-smokers may lead to increased risk for obesity and other health problems, potentially limiting the benefit of quitting smoking. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of nicotine self-administration and withdrawal on concurrently available chow and sucrose intake in adult male rats

PubMed Central

Bunney, Patricia E.; Burroughs, Danielle; Hernandez, Christine; LeSage, Mark G

2016-01-01

Carbohydrate intake, preference, and taste thresholds may be altered in current and former cigarette smokers, which may mediate weight gain and risk for obesity in individuals who quit smoking. Attempts to model these effects in rodents have primarily used noncontingent nicotine administration. The purpose of this research was to characterize changes in chow and sucrose intake in rats during a 23-h access model of i.v. nicotine self-administration (NSA), in which rats lever-pressed for chow, sucrose, and nicotine under concurrent fixed-ratio (FR) 1 schedules. Male rats were assigned to one of three groups that differed in food and drug availability. The Nicotine C+S group had concurrent access to nicotine, chow, and sucrose. The Saline C+S group had access to saline, chow, and sucrose. The Nicotine C-Only group had access to nicotine and chow, but not sucrose. Changes in food intake and weight gain were assessed during baseline, NSA, and nicotine withdrawal (i.e., saline extinction). Weight gain was significantly slowed during NSA and increased during withdrawal, but did not differ between the nicotine groups. NSA produced a significant decrease in both chow and sucrose intake. Gradual tolerance to nicotine’s effects on sucrose, but not chow intake, occurred. During withdrawal, chow and sucrose intake increased, with a larger percent increase in sucrose intake compared to chow. The proportion of total food intake from sucrose was greater at the end of withdrawal compared to baseline, indicating a history of nicotine intake changed dietary preference. Combined, these results indicate that sucrose intake is more resistant to nicotine’s appetite suppressant effects and withdrawal from nicotine produces a greater increase in sweet food intake alongside general increases in chow intake. Changes in overall food intake in current and ex-smokers may lead to increased risk for obesity and other health problems, potentially limiting the benefit of quitting smoking. PMID:26548500

Nabilone therapy for cannabis withdrawal presenting as protracted nausea and vomiting.

PubMed

Lam, Philip W; Frost, David W

2014-09-22

Cannabis is one of the most commonly used recreational drugs worldwide. Psychoactive properties of the principal compound, δ-9-tetrahydrocannabinol include euphoria, a sense of relaxation and increased appetite. Chronic cannabis use has been associated with the development of a withdrawal syndrome on abrupt discontinuation. Withdrawal symptoms typically begin within 24 h of abstinence and manifest as irritability, nervousness, sleep disturbances and decreased appetite. There is growing evidence that supports the use of plant-derived and synthetic cannabinoids for the treatment of cannabis withdrawal. In this case report, we present 20-year-old woman who developed protracted nausea and vomiting secondary to cannabis withdrawal and was successfully treated with nabilone. Nausea and vomiting is not listed in the Diagnostic and Statistical Manual-5 diagnostic criteria for cannabis withdrawal syndrome and is an uncommon symptom presentation. 2014 BMJ Publishing Group Ltd.

NMR structural study of the prototropic equilibrium in solution of Schiff bases as model compounds.

PubMed

Ortegón-Reyna, David; Garcías-Morales, Cesar; Padilla-Martínez, Itzia; García-Báez, Efren; Aríza-Castolo, Armando; Peraza-Campos, Ana; Martínez-Martínez, Francisco

2013-12-31

An NMR titration method has been used to simultaneously measure the acid dissociation constant (pKa) and the intramolecular NHO prototropic constant ΔKNHO on a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho-hydroxyaldehydes, appropriately substituted with electron-donating and electron-withdrawing groups to modulate the acidity of the intramolecular NHO hydrogen bond. The structure in solution was established by 1H-, 13C- and 15N-NMR spectroscopy. The physicochemical parameters of the intramolecular NHO hydrogen bond (pKa, ΔKNHO and ΔΔG°) were obtained from 1H-NMR titration data and pH measurements. The Henderson-Hasselbalch data analysis indicated that the systems are weakly acidic, and the predominant NHO equilibrium was established using Polster-Lachmann δ-diagram analysis and Perrin model data linearization.

Substituent effects in double-helical hydrogen-bonded AAA-DDD complexes.

PubMed

Wang, Hong-Bo; Mudraboyina, Bhanu P; Wisner, James A

2012-01-27

Two series of DDD and AAA hydrogen-bond arrays were synthesized that form triply-hydrogen-bonded double-helical complexes when combined in CDCl(3) solution. Derivatization of the DDD arrays with electron-withdrawing groups increases the complex association constants by up to a factor of 30 in those arrays examined. Derivatization of the AAA arrays with electron donating substituents reveals a similar magnitude effect on the complex stabilities. The effect of substitution on both types of arrays are modeled quite satisfactorily (R(2) > 0.96 in all cases) as free energy relationships with respect to the sums of their Hammett substituent constants. In all, the complex stabilities can be manipulated over more than three orders of magnitude (>20 kJ mol(-1)) using this type of modification. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estimated withdrawals from principal aquifers in the United States, 2000

USGS Publications Warehouse

Maupin, Molly A.; Barber, Nancy L.

2005-01-01

Fresh ground-water withdrawals from 66 principal aquifers in the United States were estimated for irrigation, public-supply, and self-supplied industrial water uses for the year 2000. Total ground-water withdrawals were 76,500 million gallons per day, or 85,800 thousand acre-feet per year for these three uses. Irrigation used the largest amount of ground water, 56,900 million gallons per day, followed by public supply with 16,000 million gallons per day, and self-supplied industrial with 3,570 million gallons per day. These three water uses represented 92 percent of the fresh groundwater withdrawals for all uses in the United States, the remaining 8 percent included self-supplied domestic, aquaculture, livestock, mining, and thermoelectric power uses. Aquifer withdrawals were categorized by five lithologic groups: unconsolidated and semiconsolidated sand and gravel aquifers, carbonate-rock aquifers, igneous and metamorphic-rock aquifers, sandstone aquifers, and sandstone and carbonate-rock aquifers. Withdrawals from aquifers that were not included in one of the 66 principal aquifers were reported in an “Other” aquifers group. The largest withdrawals in the United States were from unconsolidated and semiconsolidated sand and gravel aquifers, which accounted for 80 percent of total withdrawals from all aquifers. Carbonate-rock aquifers provided 8 percent of the withdrawals, and igneous and metamorphic-rock aquifers, 6 percent. Withdrawals from sandstone aquifers, from sandstone and carbonate-rock aquifers, and from the “Other” aquifers category each constituted about 2 percent of the total withdrawals reported.Fifty-five percent of the total withdrawals for irrigation, public-supply, and self-supplied industrial water uses were provided by the High Plains aquifer, California Central Valley aquifer system, the Mississippi River Valley alluvial aquifer, and the Basin and Range basin-fill aquifers. These aquifers provided most of the withdrawals for irrigation. The High Plains aquifer was the most intensively used aquifer in the United States. This aquifer provided 23 percent of the total withdrawals from all aquifers for irrigation, public-supply, and self-supplied industrial water uses combined, and 30 percent of the total withdrawals from all aquifers for irrigation. The primary aquifers used for public supply were the glacial sand and gravel aquifers of the Northeastern and North-Central States, the California Coastal Basin aquifers, the Floridan aquifer system, the Basin and Range basin-fill aquifers, and the Coastal lowlands aquifer system along the Gulf Coast. These five aquifers provided 43 percent of the total withdrawals from all aquifers for public supply. The glacial sand and gravel aquifers, Coastal lowlands aquifer system, Floridan aquifer system, and Cambrian-Ordovician aquifer system were the primary sources of water for self-supplied industrial use; these aquifers provided 46 percent of the total ground-water withdrawals for that use.

Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading

PubMed Central

Garcia-Alcala, Hector; Santos Vichido, Celia Isabel; Islas Macedo, Silverio; Genestier-Tamborero, Christelle Nathalie; Minutti-Palacios, Marissa; Hirales Tamez, Omara; García, Carlos; Ziegler, Dan

2015-01-01

Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA) over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid) for 4 weeks (phase 1). Subsequently, responders were randomized to receive ALA (600 mg qd; n = 16) or to ALA withdrawal (n = 17) for 16 weeks (phase 2). During phase 1, the Total Symptom Score (TSS) decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p < 0.05) and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p < 0.05). In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid) administration of ALA, subsequent treatment with ALA (600 mg qd) over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879. PMID:26345602

Comparison of efficacy between buprenorphine and tramadol in the detoxification of opioid (heroin)-dependent subjects.

PubMed

Chawla, Jatinder Mohan; Pal, Hemraj; Lal, Rakesh; Jain, Raka; Schooler, Nina; Balhara, Yatan Pal Singh

2013-01-01

Tramadol is a synthetic opiate and a centrally acting weak m-opioid receptor agonist. The potential advantages of tramadol include ease of administration, low abuse potential, and being nonscheduled. This study compared tramadol and buprenorphine for controlling withdrawal symptoms in patients with opioid dependence syndrome. Consenting male subjects between 20 and 45 years of age who fulfilled the ICD-10-DCR criteria for opiate dependence syndrome were randomly assigned in a double-blind, double-dummy placebo-controlled trial for detoxification. Those with multiple drug dependence, abnormal cardiac, renal and hepatic functions, psychosis, or organic mental illness were excluded. Assessments included Subjective Opiate Withdrawal Scale (SOWS), Objective Opiate Withdrawal Scale (OOWS), Visual Analog Scale (VAS), and Side Effect Check List. Subjects were evaluated daily and study duration was 10 days. Sixty two subjects were enrolled. The mean SOWS and OOWS and VAS were significantly lower in the buprenorphine group on second and third day of detoxification as compared to the tramadol group. Although the retention rate was higher for buprenorphine group throughout the study, when compared with tramadol the difference was not significant on any day. Three subjects in the tramadol group had seizures. Tramadol was found to have limited detoxification efficacy in moderate to severe opioid withdrawal and substantial risk of seizures as compared to buprenorphine. Further studies are warranted to examine its efficacy in mild opioid withdrawal symptoms and its potential use in outpatient settings where its administration advantages may be valuable.

Levetiracetam for the treatment of alcohol withdrawal syndrome: a multicenter, prospective, randomized, placebo-controlled trial.

PubMed

Richter, Christoph; Hinzpeter, Axel; Schmidt, Folkhard; Kienast, Thorsten; Preuss, Ulrich W; Plenge, Thomas; Heinz, Andreas; Schaefer, Martin

2010-12-01

Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS. One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale. Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups. Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

Comparing shame in clinical and nonclinical populations: Preliminary findings.

PubMed

Dyer, Kevin F W; Dorahy, Martin J; Corry, Mary; Black, Rebecca; Matheson, Laura; Coles, Holly; Curran, David; Seager, Lenaire; Middleton, Warwick

2017-03-01

To conduct a preliminary study comparing different trauma and clinical populations on types of shame coping style and levels of state shame and guilt. A mixed independent groups/correlational design was employed. Participants were recruited by convenience sampling of 3 clinical populations-complex trauma (n = 65), dissociative identity disorder (DID; n = 20), and general mental health (n = 41)-and a control group of healthy volunteers (n = 125). All participants were given (a) the Compass of Shame Scale, which measures the four common shame coping behaviors/styles of "withdrawal," "attack self," "attack other," and "avoidance," and (b) the State Shame and Guilt Scale, which assesses state shame, guilt, and pride. The DID group exhibited significantly higher levels of "attack self," "withdrawal," and "avoidance" relative to the other groups. The complex trauma and general mental health groups did not differ on any shame variable. All three clinical groups had significantly greater levels of the "withdrawal" coping style and significantly impaired shame/guilt/pride relative to the healthy volunteers. "Attack self" emerged as a significant predictor of increased state shame in the complex trauma, general mental health, and healthy volunteer groups, whereas "withdrawal" was the sole predictor of state shame in the DID group. DID emerged as having a different profile of shame processes compared to the other clinical groups, whereas the complex trauma and general mental health groups had comparable shame levels and variable relationships. These differential profiles of shame coping and state shame are discussed with reference to assessment and treatment. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

How physician electronic health record screen sharing affects patient and doctor non-verbal communication in primary care.

PubMed

Asan, Onur; Young, Henry N; Chewning, Betty; Montague, Enid

2015-03-01

Use of electronic health records (EHRs) in primary-care exam rooms changes the dynamics of patient-physician interaction. This study examines and compares doctor-patient non-verbal communication (eye-gaze patterns) during primary care encounters for three different screen/information sharing groups: (1) active information sharing, (2) passive information sharing, and (3) technology withdrawal. Researchers video recorded 100 primary-care visits and coded the direction and duration of doctor and patient gaze. Descriptive statistics compared the length of gaze patterns as a percentage of visit length. Lag sequential analysis determined whether physician eye-gaze influenced patient eye gaze, and vice versa, and examined variations across groups. Significant differences were found in duration of gaze across groups. Lag sequential analysis found significant associations between several gaze patterns. Some, such as DGP-PGD ("doctor gaze patient" followed by "patient gaze doctor") were significant for all groups. Others, such DGT-PGU ("doctor gaze technology" followed by "patient gaze unknown") were unique to one group. Some technology use styles (active information sharing) seem to create more patient engagement, while others (passive information sharing) lead to patient disengagement. Doctors can engage patients in communication by using EHRs in the visits. EHR training and design should facilitate this. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years.

PubMed

Park, Soochul; Lee, Dong Hyun; Kim, Seung Woo; Roh, Yun Ho

2017-01-01

We performed a retrospective, prognostic analysis of a cohort of patients with epilepsy according to time of relapse after four seizure-free years. Planned withdrawal of antiepileptic drugs (AEDs) and at least 3 years of follow-up after AED discontinuation were performed. The following two groups were assessed: (1) an early relapse (ER) group of patients who experienced recurrence during AED withdrawal and (2) a late relapse (LR) group of patients who experienced recurrence after completion of the AED discontinuation process. After dichotomization, the relapse rate, prognostic factors, and their impacts for each group were compared with those of a group of patients who continued to be seizure-free after AED withdrawal (SF group) using multiple logistic regression analysis. The AED intake mode was also analyzed. Two hundred seventeen (64.6%) of the 336 total patients experienced relapse. One hundred thirty-nine patients (41.4%) and 78 patients (23.2%) were included in the LR and ER groups, respectively. Symptom duration >120 months showed the strongest negative prognostic impact as demonstrated by the 4.7-fold higher risk of recurrence in the ER group compared with the SF group. Additional factors with a negative prognostic impact included an age at epilepsy onset of ≤20 years and the presence of localization-related epilepsy. No reliable predictor between the SF and LR groups was revealed. After exclusion of the SF group, post hoc analysis according to age at epilepsy onset and symptom duration showed that the above-mentioned negative prognostic factors significantly affected the relapse patterns of the LR and ER groups. The results suggest that longer symptom duration, which could be associated with intrinsic reactivation of epilepsy, is the strongest negative prognostic factor for relapse. Relapse after AED withdrawal in prolonged follow-up of seizure-free patients is one aspect of the natural history of epilepsy. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Observation of inductive effects that cause a change in the rate-determining step for the conversion of rhenium azides to imido complexes.

PubMed

Travia, Nicholas E; Xu, Zhenggang; Keith, Jason M; Ison, Elon A; Fanwick, Phillip E; Hall, Michael B; Abu-Omar, Mahdi M

2011-10-17

The cationic oxorhenium(V) complex [Re(O)(hoz)(2)(CH(3)CN)][B(C(6)F(5))(4)] [1; Hhoz = 2-(2'-hydroxyphenyl)-2-oxazoline] reacts with aryl azides (N(3)Ar) to give cationic cis-rhenium(VII) oxoimido complexes of the general formula [Re(O)(NAr)(hoz)(2)][B(C(6)F(5))(4)] [2a-2f; Ar = 4-methoxyphenyl, 4-methylphenyl, phenyl, 3-methoxyphenyl, 4-chlorophenyl, and 4-(trifluoromethyl)phenyl]. The kinetics of formation of 2 in CH(3)CN are first-order in both azide (N(3)Ar) and oxorhenium(V) complex 1, with second-order rate constants ranging from 3.5 × 10(-2) to 1.7 × 10(-1) M(-1) s(-1). A strong inductive effect is observed for electron-withdrawing substituents, leading to a negative Hammett reaction constant ρ = -1.3. However, electron-donating substituents on phenyl azide deviate significantly from this trend. Enthalpic barriers (ΔH(‡)) determined by the Eyring-Polanyi equation are in the range 14-19 kcal mol(-1) for all aryl azides studied. However, electron-donating 4-methoxyphenyl azide exhibits a large negative entropy of activation, ΔS(‡) = -21 cal mol(-1) K(-1), which is in sharp contrast to the near zero ΔS(‡) observed for phenyl azide and 4-(trifluoromethyl)phenyl azide. The Hammett linear free-energy relationship and the activation parameters support a change in the mechanism between electron-withdrawing and electron-donating aryl azides. Density functional theory predicts that the aryl azides coordinate via N(α) and extrude N(2) directly. For the electron-withdrawing substituents, N(2) extrusion is rate-determining, while for the electron-donating substituents, the rate-determining step becomes the initial attack of the azide. The barriers for these two steps are inverted in their order with respect to the Hammett σ values; thus, the Hammett plot appears with a break in its slope.

Effects of acute caffeine withdrawal on Short Category Test performance in sleep-deprived individuals.

PubMed

Killgore, William D S; Kahn-Greene, Ellen T; Killgore, Desiree B; Kamimori, Gary H; Balkin, Thomas J

2007-12-01

Caffeine is a popular stimulant often used to counter the effects of sleep loss and fatigue. Withdrawal from caffeine may produce mild declines in simple cognitive capacities such as attention and concentration, but it is unclear whether more complex cognitive functions, such as abstract reasoning or concept formation, may be similarly affected. To assess the effect of acute caffeine withdrawal on executive functioning during sleep deprivation, 26 healthy volunteers were administered in double-blind form either repeated doses of caffeine or placebo over two nights of continuous wakefulness. The 108-item Short Category Test was administered after 56 hr. of total sleep deprivation (9 hr. post-caffeine administration). The caffeine group scored significantly more poorly, making approximately 57% more errors on the test than the placebo group. These findings suggest that acute caffeine withdrawal during prolonged sleep deprivation has an adverse effect on abstract reasoning and concept formation.

Trajectories of Social Withdrawal from Middle Childhood to Early Adolescence

PubMed Central

Oh, Wonjung; Bowker, Julie C.; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

2013-01-01

Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N=392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend’s withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class. PMID:18193479

Trajectories of social withdrawal from middle childhood to early adolescence.

PubMed

Oh, Wonjung; Rubin, Kenneth H; Bowker, Julie C; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

2008-05-01

Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N = 392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend's withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class.

Modulation of ethanol withdrawal-induced anxiety-like behavior during later withdrawals by treatment of early withdrawals with benzodiazepine/gamma-aminobutyric acid ligands.

PubMed

Knapp, Darin J; Overstreet, David H; Breese, George R

2005-04-01

Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal-associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of gamma-aminobutyric acid-modulating drugs on social interaction behavior-an established model of anxiety-in rats exposed to repeated cycles of ethanol treatment and withdrawal. Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl-6, 7-dymerhoxy-4-ethyl-beta-carboline-3-carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Single-dose administration of drugs that enhance or diminish activity at benzodiazepine-gamma-aminobutyric acid- receptors during earlier withdrawals reduced or potentiated, respectively, anxiety-like behavior during later, drug-free withdrawals. These results support the potential of the novel strategy of using prophylactic therapy administered during early withdrawals to ameliorate symptoms of later withdrawals.

Electron Transport and Nonlinear Optical Properties of Substituted Aryldimesityl Boranes: A DFT Study

PubMed Central

Pandith, Altaf Hussain; Islam, Nasarul

2014-01-01

A comprehensive theoretical study was carried out on a series of aryldimesityl borane (DMB) derivatives using Density Functional theory. Optimized geometries and electronic parameters like electron affinity, reorganization energy, frontiers molecular contours, polarizability and hyperpolarizability have been calculated by employing B3PW91/6-311++G (d, p) level of theory. Our results show that the Hammett function and geometrical parameters correlates well with the reorganization energies and hyperpolarizability for the series of DMB derivatives studied in this work. The orbital energy study reveals that the electron releasing substituents increase the LUMO energies and electron withdrawing substituents decrease the LUMO energies, reflecting the electron transport character of aryldimesityl borane derivatives. From frontier molecular orbitals diagram it is evident that mesityl rings act as the donor, while the phenylene and Boron atom appear as acceptors in these systems. The calculated hyperpolarizability of secondary amine derivative of DMB is 40 times higher than DMB (1). The electronic excitation contributions to the hyperpolarizability studied by using TDDFT calculation shows that hyperpolarizability correlates well with dipole moment in ground and excited state and excitation energy in terms of the two-level model. Thus the results of these calculations can be helpful in designing the DMB derivatives for efficient electron transport and nonlinear optical material by appropriate substitution with electron releasing or withdrawing substituents on phenyl ring of DMB system. PMID:25479382

Ondansetron does not prevent physical dependence in patients taking opioid medications chronically for pain control.

PubMed

Chu, Larry F; Rico, Tom; Cornell, Erika; Obasi, Hannah; Encisco, Ellen M; Vertelney, Haley; Gamble, Jamison G; Crawford, Clayton W; Sun, John; Clemenson, Anna; Erlendson, Matthew J; Okada, Robin; Carroll, Ian; Clark, J David

2018-02-01

In this study, we investigated the co-administration of ondansetron with morphine, and whether it could prevent the development of physical dependence in patients taking opioids for the treatment of chronic pain. A total of 48 chronic back pain patients (N = 48) participated in this double-blinded, placebo-controlled, randomized study. Patients were titrated onto sustained-release oral morphine and randomized to take 8 mg ondansetron or placebo three times daily concurrently with morphine during the 30-day titration. Following titration, patients underwent Naloxone induced opioid withdrawal. Opioid withdrawal signs and symptoms were then assessed by a blinded research assistant (objective opioid withdrawal score: OOWS) and by the research participant (subjective opioid withdrawal score: SOWS). We observed clinically significant signs of naloxone-precipitated opioid withdrawal in all participants (ΔOOWS = 4.3 ± 2.4, p < 0.0001; ΔSOWS = 14.1 ± 11.7, p < 0.0001), however no significant differences in withdrawal scores were detected between treatment groups. We hypothesized that ondansetron would prevent the development of physical dependence in human subjects when co-administered with opioids, but found no difference in naloxone-precipitated opioid withdrawal scores between ondansetron and placebo treatment groups. These results suggest that further studies are needed to determine if 5HT 3 receptor antagonists are useful in preventing opioid physical dependence. Copyright © 2017 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Daniel P.; Tymińska, Nina; Zurek, Eva, E-mail: ezurek@buffalo.edu

Dispersion corrected Density Functional Theory calculations were employed to study the adsorption of benzenes derivatized with functional groups encompassing a large region of the activated/deactivated spectrum to the Ag(111) surface. Benzenes substituted with weak activating or deactivating groups, such as methyl and fluoro, do not have a strong preference for adsorbing to a particular site on the substrate, with the corrugations in the potential energy surface being similar to those of benzene. Strong activating (N(CH{sub 3}){sub 2}) and deactivating (NO{sub 2}) groups, on the other hand, possess a distinct site preference. The nitrogen in the former prefers to lie abovemore » a silver atom (top site), but in the latter a hollow hexagonal-closed-packed (H{sub hcp}) site of the Ag(111) surface is favored instead. Benzenes derivatized with classic activating groups donate electron density from their highest occupied molecular orbital to the surface, and those functionalized with deactivating groups withdraw electron density from the surface into orbitals that are unoccupied in the gas phase. For benzenes functionalized with two substituents, the groups that are strongly activating or deactivating control the site preference and the other groups assume sites that are, to a large degree, dictated by their positions on the benzene ring. The relative stabilities of the ortho, meta, and para positional isomers of disubstituted benzenes can, in some cases, be modified by adsorption to the surface.« less

Design, synthesis and structure-activity relationship of indoxacarb analogs as voltage-gated sodium channel blocker.

PubMed

Hao, Wenbo; Fu, Chunling; Yu, Huijuan; Chen, Jian; Xu, Hanhong; Shao, Guang; Jiang, Dingxin

2015-10-15

Indoxacarb, the first commercialized pyrazoline-type sodium-channel blocker, is a commonly used insecticide because of high selectivity. To discover sodium-channel blocker with high insecticidal activity, a series of novel indoxacarb analogs were designed and synthesized by judicious structural modifications of the substituent group of C5, C6 in indenone and C'4 in benzene ring. Some analogs exhibited significant insecticidal activities against Spodoptera litura F. and excellent BgNav1-1a channel inhibitory activity. The structure-activity analysis indicated that the presence of strong electron-withdrawing group and decreased steric hindrance of indenone ring (R(1), R(2)) in 5- and 6-position could enhance larvicidal activity and BgNav1-1a channel inhibitory activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Attitudes and Approaches for Withdrawing Drugs for Children with Clinically Inactive Nonsystemic JIA: A Survey of the Childhood Arthritis and Rheumatology Research Alliance.

PubMed

Horton, Daniel B; Onel, Karen B; Beukelman, Timothy; Ringold, Sarah

2017-03-01

To assess the attitudes and strategies of pediatric rheumatology clinicians toward withdrawing medications for children with clinically inactive juvenile idiopathic arthritis (JIA). Members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed an anonymous electronic survey on decision making and approaches for withdrawing medications for inactive nonsystemic JIA. Data were analyzed using descriptive statistics. Of 388 clinicians in CARRA, 124 completed surveys (32%), predominantly attending pediatric rheumatologists. The most highly ranked factors in decision making for withdrawing medications were the duration of clinical inactivity, drug toxicity, duration of prior activity, patient/family preferences, joint damage, and JIA category. Diagnoses of rheumatoid factor-positive polyarthritis and persistent oligoarthritis made respondents less likely and more likely, respectively, to withdraw JIA medications. Three-quarters of respondents waited for 6-12 months of inactive disease before stopping methotrexate (MTX) or biologics, but preferences varied. There was also considerable variability in the strategies used to reduce, taper, or stop medications for clinically inactive JIA; most commonly, clinicians reported slow medication tapers lasting at least 2 months. For children receiving combination MTX-biologic therapy, 63% of respondents preferred stopping MTX first. Most clinicians reported using imaging only seldom or sometimes to guide decision making, but most were also reluctant to withdraw medications in the presence of asymptomatic imaging abnormalities suggestive of subclinical inflammation. Considerable variability exists among pediatric rheumatology clinicians regarding when and how to withdraw medications for children with clinically inactive JIA. More research is needed to identify the most effective approaches to withdraw medications and predictors of outcomes.

Computationally Designed Oligomers for High Contrast Black Electrochromic Polymers

DTIC Science & Technology

2017-05-05

SUBJECT TERMS electrochromics, DFf, TDDFT, organic electronics , oligomer, organic polymers 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF 18. NUMBER... electron -withdrawing behaviors. Another finding was that the same dication was produced regardless of the color or peak morphology of the neutral 5...radical cation states present in the chromophore upon oxidation. The two-ring electron rich dioxythiophene portions of the chromophore (EAc) and/or the

Aromatic hydroxylation by cytochrome P450: model calculations of mechanism and substituent effects.

PubMed

Bathelt, Christine M; Ridder, Lars; Mulholland, Adrian J; Harvey, Jeremy N

2003-12-10

The mechanism and selectivity of aromatic hydroxylation by cytochrome P450 enzymes is explored using new B3LYP density functional theory computations. The calculations, using a realistic porphyrin model system, show that rate-determining addition of compound I to an aromatic carbon atom proceeds via a transition state with partial radical and cationic character. Reactivity is shown to depend strongly on ring substituents, with both electron-withdrawing and -donating groups strongly decreasing the addition barrier in the para position, and it is shown that the calculated barrier heights can be reproduced by a new dual-parameter equation based on radical and cationic Hammett sigma parameters.

The roles of tertiary amine structure, background organic matter and chloramine species on NDMA formation.

PubMed

Selbes, Meric; Kim, Daekyun; Ates, Nuray; Karanfil, Tanju

2013-02-01

N-nitrosodimethylamine (NDMA), a probable human carcinogen, is a disinfection by-product that has been detected in chloraminated and chlorinated drinking waters and wastewaters. Formation mechanisms and precursors of NDMA are still not well understood. The main objectives of this study were to systematically investigate (i) the effect of tertiary amine structure, (ii) the effect of background natural organic matter (NOM), and (iii) the roles of mono vs. dichloramine species on the NDMA formation. Dimethylamine (DMA) and 20 different tertiary aliphatic and aromatic amines were carefully examined based on their functional groups attached to the basic DMA structure. The wide range (0.02-83.9%) of observed NDMA yields indicated the importance of the structure of tertiary amines, and both stability and electron distribution of the leaving group of tertiary amines on NDMA formation. DMA associated with branched alkyl groups or benzyl like structures having only one carbon between the ring and DMA structure consistently gave higher NDMA yields. Compounds with electron withdrawing groups (EWG) reacted preferentially with monochloramine, whereas compounds with electron donating group (EDG) showed tendency to react with dichloramine to form NDMA. When the selected amines were present in NOM solutions, NDMA formation increased for compounds with EWG while decreased for compounds with EDG. This impact was attributed to the competitions between NOM and amines for chloramine species. The results provided additional information to the commonly accepted mechanism for NDMA formation including chloramine species reacting with tertiary amines and the role of the leaving group on overall NDMA conversion. Copyright © 2012 Elsevier Ltd. All rights reserved.

Incidence and impact of withdrawal of life-sustaining therapies in clinical trials of severe traumatic brain injury: A systematic review.

PubMed

Leblanc, Guillaume; Boutin, Amélie; Shemilt, Michèle; Lauzier, François; Moore, Lynne; Potvin, Véronique; Zarychanski, Ryan; Archambault, Patrick; Lamontagne, François; Léger, Caroline; Turgeon, Alexis F

2018-06-01

Background Most deaths following severe traumatic brain injury follow decisions to withdraw life-sustaining therapies. However, the incidence of the withdrawal of life-sustaining therapies and its potential impact on research data interpretation have been poorly characterized. The aim of this systematic review was to assess the reporting and the impact of withdrawal of life-sustaining therapies in randomized clinical trials of patients with severe traumatic brain injury. Methods We searched Medline, Embase, Cochrane Central, BIOSIS, and CINAHL databases and references of included trials. All randomized controlled trials published between January 2002 and August 2015 in the six highest impact journals in general medicine, critical care medicine, and neurocritical care (total of 18 journals) were considered for eligibility. Randomized controlled trials were included if they enrolled adult patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) and reported data on mortality. Our primary objective was to assess the proportion of trials reporting the withdrawal of life-sustaining therapies in a publication. Our secondary objectives were to describe the overall mortality rate, the proportion of deaths following the withdrawal of life-sustaining therapies, and to assess the impact of the withdrawal of life-sustaining therapies on trial results. Results From 5987 citations retrieved, we included 41 randomized trials (n = 16,364, ranging from 11 to 10,008 patients). Overall mortality was 23% (range = 3%-57%). Withdrawal of life-sustaining therapies was reported in 20% of trials (8/41, 932 patients in trials) and the crude number of deaths due to the withdrawal of life-sustaining therapies was reported in 17% of trials (7/41, 884 patients in trials). In these trials, 63% of deaths were associated with the withdrawal of life-sustaining therapies (105/168). An analysis carried out by imputing a 4% differential rate in instances of withdrawal of life-sustaining therapies between study groups yielded different results and conclusions in one third of the trials. Conclusion Data on the withdrawal of life-sustaining therapies are incompletely reported in randomized controlled trials of patients with severe traumatic brain injury. Given the high proportion of deaths due to the withdrawal of life-sustaining therapies in severe traumatic brain injury patients, and the potential of this medical decision to influence the results of clinical trials, instances of withdrawal of life-sustaining therapies should be systematically reported in clinical trials in this group of patients.

Comparison of enteral ethanol and benzodiazepines for alcohol withdrawal in neurocritical care patients.

PubMed

Gipson, Gregory; Tran, Kim; Hoang, Cuong; Treggiari, Miriam

2016-09-01

We designed a study to evaluate the use of benzodiazepines and ethanol in patients being assessed for alcohol withdrawal and compare outcomes between the two agents. This is a retrospective chart review of patients admitted to neurocritical care or neurosurgical services who were at risk for ethanol withdrawal between June 2011 and September 2015. Patients were divided into two groups based on the first medication administered for alcohol withdrawal management, either benzodiazepine (n=50) or enteral ethanol (n=50). The primary endpoint was the maximum change in Clinical Institute Withdrawal Assessment of Alcohol scale (CIWA) score within the first 24hours. Secondary endpoints included maximum and minimum CIWA score in 5days, length of stay, and change in Glasgow Coma Scale. Study groups differed by mortality risk, level of coma at admission, and other clinical characteristics, with the ethanol group appearing less severely ill. There was no significant difference between the two groups in the maximum change in CIWA score at 24hours (-0.97, 95%CI: -3.21 to 1.27, p=0.39). Hospital and intensive care unit length of stay was 6.5 days and 1 day shorter for the ethanol group (p=0.03 and p=0.02, respectively). In summary, enteral ethanol was preferentially used in patients who are more likely to be capable of tolerating oral intake. We found that the change from baseline in CIWA score or other physiologic variables was not substantially different between the two agents. The overall utility of benzodiazepines and enteral ethanol remains unclear for this population and further study is needed to determine superiority. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of functional groups on charge transport in molecular junctions

NASA Astrophysics Data System (ADS)

Mowbray, D. J.; Jones, G.; Thygesen, K. S.

2008-03-01

Using density functional theory (DFT), we analyze the influence of five classes of functional groups, as exemplified by NO2, OCH3, CH3, CCl3, and I, on the transport properties of a 1,4-benzenedithiolate (BDT) and 1,4-benzenediamine (BDA) molecular junction with gold electrodes. Our analysis demonstrates how ideas from functional group chemistry may be used to engineer a molecule's transport properties, as was shown experimentally and using a semiempirical model for BDA [Nano Lett. 7, 502 (2007)]. In particular, we show that the qualitative change in conductance due to a given functional group can be predicted from its known electronic effect (whether it is σ /π donating/withdrawing). However, the influence of functional groups on a molecule's conductance is very weak, as was also found in the BDA experiments. The calculated DFT conductances for the BDA species are five times larger than the experimental values, but good agreement is obtained after correcting for self-interaction and image charge effects.

Susceptible alleles of the CD40 and CTLA-4 genes are not associated with the relapse after antithyroid withdrawal in Graves' disease.

PubMed

Kim, Kyung Won; Park, Young Joo; Kim, Tae Yong; Park, Do Joon; Park, Kyong Soo; Cho, Bo Youn

2007-12-01

In this study, we investigated whether the CD40 or cytotoxic T lymphocyte-associated molecules-4 (CTLA-4) polymorphisms, which are associated with the susceptibility of Graves' disease (GD), can predict the clinical outcome after antithyroid drug (ATD) withdrawal. All patients with GD were treated with ATD. GD patients were divided into two groups: remission or failure. The remission group was defined as patients who maintained a euthyroid state for 1 year after ATD withdrawal. The failure group was defined as patients who relapsed within 1 year after the discontinuation of ATD or who could not discontinue their ATD treatment within 24 months. The rate of treatment failure after ATD withdrawal was 72.2%. For the susceptible genes, the CC genotype in the CD40, the GG genotype in the CTLA-4 exon 1, and the CC genotype in the CTLA-4 promoter region have shown no significant association with a clinical outcome after ATD withdrawal. However, clinical parameters, such as male gender, severe thyrotoxicosis, high thyroid-stimulating hormone-binding inhibitory immunoglobulin value, and a large goiter, were related to treatment failure. These findings suggest that the genetic markers associated with the development of GD cannot be used to predict the relapse of GD patients in place of clinical parameters.

Regioselective Galactofuranosylation for the Synthesis of Disaccharide Patterns Found in Pathogenic Microorganisms.

PubMed

Legentil, Laurent; Cabezas, Yari; Tasseau, Olivier; Tellier, Charles; Daligault, Franck; Ferrières, Vincent

2017-07-21

Koenigs-Knorr glycosylation of acceptors with more than one free hydroxyl group by 2,3,5,6-tetrabenzoyl galactofuranosyl bromide was performed using diphenylborinic acid 2-aminoethyl ester (DPBA) as inducer of regioselectivity. High regioselectivity for the glycosylation on the equatorial hydroxyl group of the acceptor was obtained thanks to the transient formation of a borinate adduct of the corresponding 1,2-cis diol. Nevertheless formation of orthoester byproducts hampered the efficiency of the method. Interestingly electron-withdrawing groups on O-6 or on C-1 of the acceptor displaced the reaction in favor of the desired galactofuranosyl containing disaccharide. The best yield was obtained for the furanosylation of p-nitrophenyl 6-O-acetyl mannopyranoside. Precursors of other disaccharides, found in the glycocalix of some pathogens, were synthesized according to the same protocol with yields ranging from 45 to 86%. This is a good alternative for the synthesis of biologically relevant glycoconjugates.

Modification of social withdrawal through symbolic modeling1

PubMed Central

O'Connor, Robert D.

1969-01-01

The present experiment was designed to test the efficacy of symbolic modeling as a treatment to enhance social behavior in preschool isolates. Nursery school children who displayed marked social withdrawal were assigned to one of two conditions. One group observed a film depicting increasingly more active social interactions between children with positive consequences ensuing in each scene, while a narrative soundtrack emphasized the appropriate behavior of the models. A control group observed a film that contained no social interaction. Control children displayed no change in withdrawal behavior, whereas those who had the benefit of symbolic modeling increased their level of social interaction to that of non-isolate nursery school children. PMID:16795196

Synthesis and Analgesic Properties of Lidocaine Derivatives with Substituted Aminobenzothiazoles.

PubMed

Ahmadi, Abbas; Khalili, Mohsen; Mohammadinoude, Mohammad Kazem; Nahri-Niknafs, Babak

2016-01-01

Local anesthetics are the most widely consumed drugs in the practice of medicine which provide a loss of sensation in a certain body part without loss of consciousness or impairment of central control of essential functions. Lidocaine (I) is the most commonly local anaesthetic drug which is widely used in all species due to its fabulous diffusing and penetrating properties as well as prompt onset of surgical analgesia. In this study, new aminobenzothiazole (with many useful biological and pharmacological properties) analogues were synthesized by changing of amine moiety of I. Both acute and chronic pain properties of new compounds (II-VI) were studied by using the tail immersion and formalin tests on mice and the outcomes were compared with control and lidocaine groups. According to the results, aminobenzothiazole derivatives are better candidates than diethylamine group for replacement on amine moiety of I. Also, derivatives with electron-withdrawing groups on this amine (V and VI) could decrease pain better than electron-donating ones (II and III) (specially on position 6 of this amine, II and V) which may be of concern for blockade of specific sodium channels by these new compounds.

Energy level alignment and quantum conductance of functionalized metal-molecule junctions: Density functional theory versus GW calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Chengjun; Markussen, Troels; Thygesen, Kristian S., E-mail: thygesen@fysik.dtu.dk

We study the effect of functional groups (CH{sub 3}*4, OCH{sub 3}, CH{sub 3}, Cl, CN, F*4) on the electronic transport properties of 1,4-benzenediamine molecular junctions using the non-equilibrium Green function method. Exchange and correlation effects are included at various levels of theory, namely density functional theory (DFT), energy level-corrected DFT (DFT+Σ), Hartree-Fock and the many-body GW approximation. All methods reproduce the expected trends for the energy of the frontier orbitals according to the electron donating or withdrawing character of the substituent group. However, only the GW method predicts the correct ordering of the conductance amongst the molecules. The absolute GWmore » (DFT) conductance is within a factor of two (three) of the experimental values. Correcting the DFT orbital energies by a simple physically motivated scissors operator, Σ, can bring the DFT conductances close to experiments, but does not improve on the relative ordering. We ascribe this to a too strong pinning of the molecular energy levels to the metal Fermi level by DFT which suppresses the variation in orbital energy with functional group.« less

48 CFR 15.208 - Submission, modification, revision, and withdrawal of proposals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... solicitation. Offerors may use any transmission method authorized by the solicitation (i.e., regular mail, electronic commerce, or facsimile). If no time is specified in the solicitation, the time for receipt is 4:30... not unduly delay the acquisition; and— (i) If it was transmitted through an electronic commerce method...

78 FR 57456 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-18

... collection. Title: Information Regarding Request for Refund of Social Security Tax Erroneously Withheld on..., and, if applicable, consent to an electronic funds withdrawal. Affected Public: Private Sector...

Influence of environmental enrichment on hypothalamic-pituitary-adrenal (HPA) responses to single-dose nicotine, continuous nicotine by osmotic mini-pumps, and nicotine withdrawal by mecamylamine in male and female rats

PubMed Central

Skwara, Amanda J.; Karwoski, Tracy E.; Czambel, R. Kenneth; Rubin, Robert T.; Rhodes, Michael E.

2012-01-01

In the present study, we determined the effects of environmental enrichment (EE; Kong Toys® and Nestlets®) on sexually diergic HPA axis responses to single-dose nicotine (NIC), single-dose NIC following continuous NIC administration for two weeks, and NIC withdrawal by single-dose mecamylamine (MEC) in male and female rats. Blood sampling occurred before and after MEC and NIC administrations for the determination of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Supporting and extending our previous findings, EE appeared to produce anxiolytic effects by reducing hormone responses: Male and female rats housed with EE had lower baseline ACTH and significantly lower HPA axis responses to the mild stress of saline (SAL) injection than did those housed without EE. The sexually diergic responses to single dose NIC, continuous NIC, and MEC-induced NIC withdrawal were reduced by EE in many male and female groups. ACTH responses to continuous NIC and MEC-induced NIC withdrawal were blunted to a greater extent in female EE groups than in male EE groups, suggesting that females are more sensitive to the anxiolytic effects of EE. Because EE lowered stress-responsive hormones of the HPA axis in most groups, EE may be a useful intervention for stress reduction in animal models of NIC addiction. As well, the effectiveness of EE in animal studies of NIC withdrawal may enlighten human studies addressing coping styles and tobacco cessation in men and women. PMID:22705101

Modulation of Ethanol Withdrawal–Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/γ-Aminobutyric Acid Ligands

PubMed Central

Knapp, Darin J.; Overstreet, David H.; Breese, George R.

2010-01-01

Background Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal–associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of γ-aminobutyric acid–modulating drugs on social interaction behavior—an established model of anxiety—in rats exposed to repeated cycles of ethanol treatment and withdrawal. Methods Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl–6, 7–dymerhoxy–4–ethyl–beta–carboline–3–carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Results Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Conclusions Single-dose administration of drugs that enhance or diminish activity at benzodiazepine–γ-aminobutyric acid- receptors during earlier withdrawals reduced or potentiated, respectively, anxiety-like behavior during later, drug-free withdrawals. These results support the potential of the novel strategy of using prophylactic therapy administered during early withdrawals to ameliorate symptoms of later withdrawals. PMID:15834220

DIFFERENTIAL EFFECTS OF SINGLE VERSUS REPEATED ALCOHOL WITHDRAWAL ON THE EXPRESSION OF ENDOCANNABINOID SYSTEM-RELATED GENES IN THE RAT AMYGDALA

PubMed Central

Serrano, Antonia; Rivera, Patricia; Pavon, Francisco J.; Decara, Juan; Suárez, Juan; de Fonseca, Fernando Rodriguez; Parsons, Loren H.

2011-01-01

Background Endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) exert important regulatory influences on neuronal signaling, participate in short- and long-term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity and affective control. Methods The consequence of long-term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT-PCR analyses of amygdala tissue. Two groups of ethanol-exposed rats were generated by maintenance on an ethanol liquid diet (10%): one group received continuous access to ethanol for 15 days, while the second group was given intermittent access to the ethanol diet (5 days/week for 3 weeks). Control subjects were maintained on an isocaloric ethanol-free liquid diet. To provide an initial profile of acute withdrawal amygdala tissue was harvested following either 6 or 24 hours of ethanol withdrawal. Results Acute ethanol withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2-AG (FAAH and MAGL, respectively) were evident, as were reductions in mRNA expression for CB1, CB2 and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent ethanol exposure, alterations in MAGL and cannabinoid receptor-related mRNA (e.g. CB1, CB2, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal-associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in 2-AG biosynthesis (e.g. DAGL-α/β) were found in any condition. Conclusions These findings suggest that ethanol dependence and withdrawal are associated with dysregulated endocannabinoid signaling in the amygdala. These alterations may contribute to withdrawal-related dysregulation of amygdalar neurotransmission. PMID:22141465

Anhedonia: Its Dynamic Relations With Craving, Negative Affect, and Treatment During a Quit Smoking Attempt.

PubMed

Cook, Jessica W; Lanza, Stephanie T; Chu, Wanghuan; Baker, Timothy B; Piper, Megan E

2017-06-01

Research shows that abstinence from tobacco leads to a withdrawal-related decrement in responsivity to nondrug rewards (ie, anhedonia). However, it remains unclear how anhedonia relates to other key withdrawal symptoms and withdrawal-related constructs over time. We analyzed ecological momentary assessment data to examine whether a decrement in response to rewards during a 10-day period following quitting shows a pattern of associations with other variables (ie, treatment, tobacco dependence, negative affect, and craving) that is consistent with anhedonia being a tobacco withdrawal symptom. As part of a randomized controlled trial of smoking cessation therapies, 1122 adults (58% female) were assigned to: placebo (n = 131), bupropion (alone or with nicotine lozenge; n = 401), or nicotine replacement therapy (NRT; lozenge, patch, both; n = 590). Participants completed 4 ecological momentary assessments per day for 10 days postquit, resulting in 22 575 assessments. Time-varying effect modeling showed that anhedonia was significantly greater among those high in dependence relative to lower dependent smokers out to day 9 postquit. The placebo group showed elevated anhedonia immediately postquit, which fell to levels similar to the treatment groups by day 7. NRT effectively reduced anhedonia and its time-varying association with craving early in the quit attempt. The positive association between negative affect and anhedonia was moderate and stable over time for both active treatment groups. These results provide additional support that anhedonia following quitting smoking is a manifestation of the tobacco withdrawal syndrome. This study supported the hypothesis that diminished responsivity to nondrug rewards (ie, anhedonia) is a symptom of the tobacco withdrawal syndrome. Results showed that anhedonia: (1) was significantly associated with dependence, especially during the early postquit period when withdrawal was at its peak intensity; (2) showed significant time-varying associations with other withdrawal symptoms, especially craving; and (3) was significantly suppressed by agonist administration as was its association with craving over time. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cost-utility of medication withdrawal in older fallers: results from the improving medication prescribing to reduce risk of FALLs (IMPROveFALL) trial.

PubMed

Polinder, Suzanne; Boyé, Nicole D A; Mattace-Raso, Francesco U S; Van der Velde, Nathalie; Hartholt, Klaas A; De Vries, Oscar J; Lips, Paul; Van der Cammen, Tischa J M; Patka, Peter; Van Beeck, Ed F; Van Lieshout, Esther M M

2016-11-04

The use of Fall-Risk-Increasing-Drugs (FRIDs) has been associated with increased risk of falls and associated injuries. This study investigates the effect of withdrawal of FRIDs versus 'care as usual' on health-related quality of life (HRQoL), costs, and cost-utility in community-dwelling older fallers. In a prospective multicenter randomized controlled trial FRIDs assessment combined with FRIDs-withdrawal or modification was compared with 'care as usual' in older persons, who visited the emergency department after experiencing a fall. For the calculation of costs the direct medical costs (intramural and extramural) and indirect costs (travel costs) were collected for a 12 month period. HRQoL was measured at baseline and at 12 months follow-up using the EuroQol-5D and Short Form-12 version 2. The change in EuroQol-5D and Short Form-12 scores over 12 months follow-up within the control and intervention groups was compared using the Wilcoxon Signed Rank test for continuous variables and the McNemar test for dichotomous variables. The change in scores between the control and intervention groups were compared using a two-way analysis of variance. We included 612 older persons who visited an emergency department because of a fall. The mean cost of the FRIDs intervention was €120 per patient. The total fall-related healthcare costs (without the intervention costs) did not differ significantly between the intervention group and the control group (€2204 versus €2285). However, the withdrawal of FRIDs reduced medication costs with a mean of €38 per participant. Furthermore, the control group had a greater decline in EuroQol-5D utility score during the 12-months follow-up than the intervention group (p = 0.02). The change in the Short Form-12 Physical Component Summary and Mental Component Summary scores did not differ significantly between the two groups. Withdrawal of FRID's in older persons who visited an emergency department due to a fall, did not lead to reduction of total health-care costs. However, the withdrawal of FRIDs reduced medication costs with a mean of €38 per participant in combination with less decline in HRQoL is an important result. The trial is registered in the Netherlands Trial Register ( NTR1593 - October 1 st 2008).

Emergence of dormant conditioned incentive approach by conditioned withdrawal in nicotine addiction.

PubMed

Scott, Daniel; Hiroi, Noboru

2010-10-15

Nicotine is one of the determinants for the development of persistent smoking, and this maladaptive behavior is characterized by many symptoms, including withdrawal and nicotine seeking. The process by which withdrawal affects nicotine seeking is poorly understood. The impact of a withdrawal-associated cue on nicotine (.2 mg/kg)-conditioned place preference was assessed in male C57BL/6J mice (n = 8-17/group). To establish a cue selectively associated with withdrawal distinct from those associated with nicotine, a tone was paired with withdrawal in their home cages; mice were chronically exposed to nicotine (200 μg/mL for 15 days) from drinking water in their home cages and received the nicotinic acetylcholine receptor antagonist mecamylamine (2.5 mg/kg) to precipitate withdrawal in the presence of a tone. The effect of the withdrawal-associated tone on nicotine-conditioned place preference was then evaluated in the place-conditioning apparatus after a delay, when nicotine-conditioned place preference spontaneously disappeared. A cue associated with precipitated withdrawal reactivated the dormant effect of nicotine-associated cues on conditioned place preference. This effect occurred during continuous exposure to nicotine but not during abstinence. A conditioned withdrawal cue could directly amplify the incentive properties of cues associated with nicotine. This observation extends the contemporary incentive account of the role of withdrawal in addiction to cue-cue interaction. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Density Functional Study on A-Units Based on Thieno[3,4- c]pyrrole-4,6-dione for Organic Solar Cells

NASA Astrophysics Data System (ADS)

Tang, Xiaoqin; Shen, Wei; Fu, Zhiyong; Liu, Xiaorui; Li, Ming

2017-08-01

The use of polymer donor materials has allowed great progress in organic solar cells. To search for potential donor materials, we have designed a series of donor-acceptor (D-A)-type alternating polymers composed of dithieno[3,2- b:2',3'- d]pyrrole (DTP) electron-rich units and thieno[3,4- c]pyrrole-4,6-dione (TPD) electron-deficient units. Their electronic and optical properties have been investigated using density functional theory and Marcus theory. The calculation results demonstrate that introduction of cyclic compounds (furyl, thienyl, and phenyl) into electron-deficient units of the molecules can result in lower highest occupied molecular orbital (HOMO) levels and reorganization energies compared with the experimental molecule ( X 0 ). To investigate the effects of electron-withdrawing units, three electron-withdrawing substituents (-OCH3, -F, and -CN) were introduced into the thienyl. The results indicated that the polymer X 2-3 will show the best performance among the designed polymers, offering low-lying HOMO energy level (-5.47 eV), narrow energy gap (1.97 eV), and high hole mobility (7.45 × 10-2 cm2 V-1 s-1). This work may provide a guideline for the design of efficient D-A polymers for organic solar cells with enhanced performance.

Suzuki–Miyaura Cross-Coupling of Aryl Carbamates and Sulfamates: Experimental and Computational Studies

PubMed Central

Quasdorf, Kyle W.; Antoft-Finch, Aurora; Liu, Peng; Silberstein, Amanda L.; Komaromi, Anna; Blackburn, Tom; Ramgren, Stephen D.; Houk, K. N.; Snieckus, Victor; Garg, Neil K.

2011-01-01

The first Suzuki–Miyaura cross-coupling reactions of the synthetically versatile O-aryl carbamate and O-sulfamate groups is described. The transformations utilize the inexpensive, bench-stable catalyst NiCl2(PCy3)2 to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups (EDGs, EWGs) are tolerated, in addition to those that possess ortho substitutents. Furthermore, heteroaryl substrates may be employed as coupling partners. A computational study providing the full catalytic cycles for these cross-coupling reactions is described. The oxidative additions with carbamates and sulfamates occur via a five-centered transition state, resulting in the exclusive cleavage of the Ar–O bond. Water is found to stabilize the Ni–carbamate catalyst resting state, and thus provides rationalization of the relative decreased rate of coupling of carbamates. Several synthetic applications are presented to showcase the utility of the methodology in the synthesis of polysubstituted aromatic compounds of natural product and bioactive molecule interest. PMID:21456551

Nephrologists' perceptions regarding dialysis withdrawal and palliative care in Europe: lessons from a European Renal Best Practice survey

PubMed Central

van Biesen, Wim; van de Luijtgaarden, Moniek W.M.; Brown, Edwina A.; Michel, Jean-Pierre; van Munster, Barbara C.; Jager, Kitty J.; van der Veer, Sabine N.

2015-01-01

Background There is a variation in dialysis withdrawal rates, but reasons for this variation across European countries are largely unknown. We therefore surveyed nephrologists' perceptions of factors concerning dialysis withdrawal and palliative care and explored relationships between these perceptions and reports of whether withdrawal actually occurred in practice. Methods We developed a 33-item electronic survey, disseminated via an email blast to all European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) members. In our data analyses, we distinguished those respondents who reported occurrence from those reporting no dialysis withdrawal in their unit. With multilevel logistic regression, we investigated the association between respondents' characteristics and perceptions and whether they reported occurrence of dialysis withdrawal or not. Results Five hundred and twenty-eight nephrologists from 45 countries completed the questionnaire; 42% reported occurrence of withdrawal in their unit in the past year, and 56% perceived that stopping life-prolonging treatment in terminally ill patients was allowed. Few respondents reported presence in their unit of protocols on withdrawal decision making (7%) or palliative care (10%) or the common involvement of a geriatrician in withdrawal decisions (10%). The majority stated that palliative care had not been part of their core curriculum (74%) and that they had not recently attended continuous medical education sessions on this topic (73%). Respondents from Eastern and Southern Europe had a 42 and 40% lower probability, respectively, of reporting withdrawal compared with those from North European countries. Working in a public centre [odds ratio (OR), 2.41; 95% confidence interval (CI), 1.36–4.25] and respondents' perception that stopping life-prolonging treatment in terminally ill patients was allowed (OR, 1.96; 95% CI, 1.23–3.12), that withdrawal decisions were commonly shared between doctor and patient (OR, 1.97; 95% CI, 1.26–3.08) and that palliative care was reimbursed (OR, 1.81; 95% CI, 1.16–2.83) increased the odds of reporting occurrence of withdrawal. Conclusion Reports of dialysis withdrawal occurrence varied between European countries. Occurrence reports were more likely if respondents worked in a public centre, if stopping life-prolonging treatments was perceived as allowed, if withdrawal decisions were considered shared between doctors and patients and if reimbursement of palliative care was believed to be in place. There is room for improvement regarding protocols on withdrawal and palliative care processes and regarding nephrologists' training and education on end-of-life care. PMID:26268713

Precursors of social emotional functioning among full-term and preterm infants at 12 months: Early infant withdrawal behavior and symptoms of maternal depression.

PubMed

Moe, Vibeke; Braarud, Hanne Cecilie; Wentzel-Larsen, Tore; Slinning, Kari; Vannebo, Unni Tranaas; Guedeney, Antoine; Heimann, Mikael; Rostad, Anne Margrethe; Smith, Lars

2016-08-01

This study forms part of a longitudinal investigation of early infant social withdrawal, maternal symptoms of depression and later child social emotional functioning. The sample consisted of a group of full-term infants (N=238) and their mothers, and a group of moderately premature infants (N=64) and their mothers. At 3 months, the infants were observed with the Alarm Distress Baby Scale (ADBB) and the mothers completed the Edinburgh Postnatal Depression Scale (EPDS). At 12 months, the mothers filled out questionnaires about the infants' social emotional functioning (Infant Toddler Social Emotional Assessment and the Ages and Stages Questionnaire-Social Emotional). At 3 months, as we have previously shown, the premature infants had exhibited more withdrawal behavior and their mothers reported elevated maternal depressive symptoms as compared with the full-born group. At 12 months the mothers of the premature infants reported more child internalizing behavior. These data suggest that infant withdrawal behavior as well as maternal depressive mood may serve as sensitive indices of early risk status. Further, the results suggest that early maternal depressive symptoms are a salient predictor of later child social emotional functioning. However, neither early infant withdrawal behavior, nor gestational age, did significantly predict social emotional outcome at 12 months. It should be noted that the differences in strength of the relations between ADBB and EPDS, respectively, to the outcome at 12 months was modest. An implication of the study is that clinicians should be aware of the complex interplay between early infant withdrawal and signs of maternal postpartum depression in planning ports of entry for early intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

Controlled Expansion of a Strong-Field Iron Nitride Cluster: Multi-Site Ligand Substitution as a Strategy for Activating Interstitial Nitride Nucleophilicity.

PubMed

Drance, Myles J; Mokhtarzadeh, Charles C; Melaimi, Mohand; Agnew, Douglas W; Moore, Curtis E; Rheingold, Arnold L; Figueroa, Joshua S

2018-05-02

Multimetallic clusters have long been investigated as molecular surrogates for reactive sites on metal surfaces. In the case of the μ 4 -nitrido cluster [Fe 4 (μ 4 -N)(CO) 12 ] - , this analogy is limited owing to the electron-withdrawing effect of carbonyl ligands on the iron nitride core. Described here is the synthesis and reactivity of [Fe 4 (μ 4 -N)(CO) 8 (CNAr Mes2 ) 4 ] - , an electron-rich analogue of [Fe 4 (μ 4 -N)(CO) 12 ] - , where the interstitial nitride displays significant nucleophilicity. This characteristic enables rational expansion with main-group and transition-metal centers to yield unsaturated sites. The resulting clusters display surface-like reactivity through coordination-sphere-dependent atom rearrangement and metal-metal cooperativity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Poly(trifluoromethyl)azulenes: structures and acceptor properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clikeman, Tyler T.; Bukovsky, Eric V.; Kuvychko, Igor V.

2014-07-10

Azulene is a non-alternant, non-benzenoid aromatic hydrocarbon with an intense blue colour, a dipole moment of 1.0 D,1 positive electron affinity, and an “anomalous” emission from the second excited state in violation of Kasha’s rule.2,3 Azulene’s unique properties have potential uses in molecular switches,4,5 molecular diodes,6 organic photovoltaics,7 and charge transfer complexes.8-12 Introduction of electron-withdrawing groups to the azulenic core, such as CN,8,13,14 halogens,15-19 and CF3,20,21 can enhance certain electrical and photophysical properties. In this work, we report six new trifluoromethyl derivatives of azulene (AZUL), three isomers of AZUL(CF3)3 and three isomers of AZUL(CF3)4, and the first X-ray structure ofmore » a π-stacked donor-acceptor complex of a trifluoromethyl azulene with donor pyrene.« less

Cytotoxic 2',5'-dihydroxychalcones with unexpected antiangiogenic activity.

PubMed

Nam, Nguyen-Hai; Kim, Yong; You, Young-Jae; Hong, Dong-Ho; Kim, Hwan-Mook; Ahn, Byung-Zun

2003-02-01

A series of 2',5'-dihydroxychalcones were synthesized and evaluated for cytotoxicity against tumor cell lines and human umbilical venous endothelial cells (HUVEC). It was found that chalcones with electron-withdrawing substituents on the B ring exhibited potent cytotoxicity against a variety of tumor cell lines while compounds with electron-releasing groups were less potent in general. Those compounds with B ring replaced by extended or heteroaromatic rings exhibited significant bioactivity. Several compounds were shown to have marked cytotoxic selectivity towards HUVECs. Especially, among the synthesized compounds, 2-chloro-2',5'-dihydroxychalcone (2-3) showed the highest selectivity index up to 66 in comparison to HCT116 cells. This compound also exhibited strong inhibitory effects on the HUVEC tube formation in an in vitro model. When administered into BDF1 mice bearing Lewis lung carcinoma cells at 50 mg kg(-1) day(-1), 2-3 was found to inhibit the growth of tumor mass by 60.5%.

Treatment for amphetamine withdrawal.

PubMed

Srisurapanont, M; Jarusuraisin, N; Kittirattanapaiboon, P

2001-01-01

Amphetamine withdrawal has been less studied although it is a common problem with a prevalent rate of 87% among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse of amphetamine use. In clinical practice, treatment for cocaine withdrawal has been recommended for the management of amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two substances are not the same. To search and determine risks, benefits, and costs of a variety of treatments for the management of amphetamine withdrawal. Electronic searches of MEDLINE (1966 - December 2000), EMBASE (1980 - February 2001), CINAHL (1982 - January 2001) and Cochrane Controlled Trials Register (Cochrane Library 2000 issue 4) were undertaken. References to the articles obtained by any means were searched. All relevant randomised controlled trials (RCTs) and controlled clinical trials (CCTs) were included. Participants were people with amphetamine withdrawal, diagnosed by any set of criteria. Any kinds of biological and psychological treatments both alone and combined were examined. A variety of outcomes, for example, number of treatment responders, score changes, were considered. Two reviewers evaluated and extracted the data independently. The dichotomous data were extracted on an intention-to-treat basis in which the dropouts were assigned as participants with the worst outcomes. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess the dichotomous data. The Weighted Mean Difference (WMD) with 95% CI was used to assessed the continuous data. The results of two studies have shown some benefits of amineptine in the treatment of amphetamine withdrawal. Those benefits can be seen in the respects of discontinuation rate and global state, as measured by Clinical Global Impression Scale. However, no direct benefit of amineptine on amphetamine withdrawal symptoms or craving was shown. The evidence about the treatment for amphetamine withdrawal is very limited. Amineptine has limited benefits on some amphetamine withdrawal symptoms. Due to a number of reports of amineptine abuse, it has been withdrawn from the market for a few years. At present, no available treatment has been demonstrated to be effective in the treatment of amphetamine withdrawal. The medications that should be considered for further treatment studies may be those with the propensities to increase dopamine, norepinephrine and/or serotonin activities of the brain. Naturalistic studies of amphetamine withdrawal symptoms and course are also crucial for the development of study designs appropriate for further treatment studies of amphetamine withdrawal.

Attitudes and approaches for withdrawing drugs for children with clinically inactive non-systemic JIA: a survey of the Childhood Arthritis and Rheumatology Research Alliance

PubMed Central

Horton, Daniel B.; Onel, Karen B.; Beukelman, Timothy; Ringold, Sarah

2016-01-01

Objective To assess the attitudes and strategies of pediatric rheumatology clinicians towards withdrawing medications for children with clinically inactive juvenile idiopathic arthritis (JIA). Methods Members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed an anonymous electronic survey on decision-making and approaches for withdrawing medications for inactive non-systemic JIA. Data were analyzed using descriptive statistics. Results Of 388 clinicians in CARRA, 124 completed surveys (32%), predominantly attending pediatric rheumatologists. The most highly ranked factors in decision-making for withdrawing medications were duration of clinical inactivity, drug toxicity, duration of prior activity, patient/family preferences, joint damage, and JIA category. Diagnoses of RF-positive polyarthritis and persistent oligoarthritis made respondents less likely and more likely, respectively, to withdraw JIA medications. Three-quarters of respondents waited for 6–12 months of inactive disease before stopping methotrexate or biologics, but preferences varied. There was also considerable variability in the strategies used to reduce, taper, or stop medications for clinically inactive JIA; most commonly, clinicians reported slow medication tapers lasting at least 2 months. For children on combination methotrexate-biologic therapy, 63% of respondents preferred stopping methotrexate first. Most clinicians reported using imaging only seldom or sometimes to guide decision-making, but most were also reluctant to withdraw medications in the presence of asymptomatic imaging abnormalities suggestive of subclinical inflammation. Conclusion Considerable variability exists among pediatric rheumatology clinicians regarding when and how to withdraw medications for children with clinically inactive JIA. More research is needed to identify the most effective approaches to withdraw medications and predictors of outcomes. PMID:28148696

Narp regulates long-term aversive effects of morphine withdrawal

PubMed Central

Reti, Irving M.; Crombag, Hans S.; Takamiya, Kogo; Sutton, Jeffrey M.; Guo, Ning; Dinenna, Megan L.; Huganir, Richard L.; Holland, Peter C.; Baraban, Jay M.

2008-01-01

Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. As Narp is an immediate early gene product that is secreted at synaptic sites and binds to AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, we found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, we evaluated whether long-term aversive effects of morphine withdrawal are altered in Narp KO mice. We found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than WT controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. PMID:18729628

The use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms.

PubMed

Jukić, Tomislav; Rojc, Bojan; Boben-Bardutzky, Darja; Hafner, Mateja; Ihan, Alojz

2011-12-01

We described the use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms in patients starting a detoxification therapy. Since abstinence from ethanol causes a hypodopaminergic and a hypoopioidergic environment in the reword system circuits, manifesting with withdrawal symptoms, food supplements that contains D-phenylalanine a peptidase inhibitor (of opioide inactivation) and L-amino-acids (for dopamine synthesis) were used to replenish a lack in neurotransmitters and alleviate the symptoms of alcohol withdrawal. 20 patients suffering from alcohol addictions starting a detoxification therapy have been included in a prospective, randomized, double blind study. The patients have been randomly devided in two groups. One group recieved for a period of 40 days a food supplement containing D-phenylalanine, L-glutamine and L-5-hydroxytriptophan (investigation group), and the control (placebo) group. On the first day of hospitalization the patients performed a SCL-90-R test, and blood samples were taken for measuring liver enzymes, total bilirubin, unbound cortisol and lymphocyte populations. The same was done on the 40th day of hospitalization. During the therapy a significant decrease in SCL-90-R psychiatric symptoms scores and a significant increase in CD4 lymphocyte count was observed in the investigation group. The cortisol values were significantly, but equally decreased in both groups, the same was with the liver enzymes and the total bilirubin values. We conclude that abstinence causes a major stress for the patients. The use of food supplement containing D-phenylalanine, L-glutamine and L-5-hydroxytriptophan alleviates the withdrawal symptoms and causes a rise in CD4 lymphocyte population, but it dose not affect the serum cortisol levels, which are probably more affected by liver inflammation and the liver restitution.

Reduced withdrawal and failure rates of accelerated nursing students enrolled in pharmacology is associated with a supportive intervention.

PubMed

Doggrell, Sheila Anne; Schaffer, Sally

2016-02-01

To reduce nursing shortages, accelerated nursing programs are available for domestic and international students. However, the withdrawal and failure rates from these programs may be different than for the traditional programs. The main aim of our study was to improve the retention and experience of accelerated nursing students. The academic background, age, withdrawal and failure rates of the accelerated and traditional students were determined. Data from 2009 and 2010 were collected prior to intervention. In an attempt to reduce the withdrawal of accelerated students, we set up an intervention, which was available to all students. The assessment of the intervention was a pre-post-test design with non-equivalent groups (the traditional and the accelerated students). The elements of the intervention were a) a formative website activity of some basic concepts in anatomy, physiology and pharmacology, b) a workshop addressing study skills and online resources, and c) resource lectures in anatomy/physiology and microbiology. The formative website and workshop was evaluated using questionnaires. The accelerated nursing students were five years older than the traditional students (p < 0.0001). The withdrawal rates from a pharmacology course are higher for accelerated nursing students, than for traditional students who have undertaken first year courses in anatomy and physiology (p = 0.04 in 2010). The withdrawing students were predominantly the domestic students with non-university qualifications or equivalent experience. The failure rates were also higher for this group, compared to the traditional students (p = 0.05 in 2009 and 0.03 in 2010). In contrast, the withdrawal rates for the international and domestic graduate accelerated students were very low. After the intervention, the withdrawal and failure rates in pharmacology for domestic accelerated students with non-university qualifications were not significantly different than those of traditional students. The accelerated international and domestic graduate nursing students have low withdrawal rates and high success rates in a pharmacology course. However, domestic students with non-university qualifications have higher withdrawal and failure rates than other nursing students and may be underprepared for university study in pharmacology in nursing programs. The introduction of an intervention was associated with reduced withdrawal and failure rates for these students in the pharmacology course.

The Effect of Pretreatment with Thiopental on Reducing Pain Induced by Rocuronium Injection

PubMed Central

Park, Jong-Taek; Choi, Jae-Chan; Yoo, Young-Soo; Lee, Young-Bok; Kim, Soon-Yul

2005-01-01

We examined whether pretreatment with a small dose of thiopental was effective in reducing pain induced by the intravenous injection of rocuronium. Withdrawal movement was used to assess pain reduction. Ninety patients were randomly assigned to one of two groups: patients in the control group were pretreated with 2 mL saline, and those in the thiopental group were pretreated with 2 mL (50 mg) thiopental. Thiopental 5 mg/kg was injected intravenously. After a loss of consciousness, the upper arm was compressed with a rubber tourniquet, and the pretreatment drugs were administered. Thirty seconds later the tourniquet was removed and 0.6 mg/kg rocuronium was administered. Withdrawal movement was assessed using a four-grade scale: no movement, movement limited to the wrist, to the elbow or to the shoulder. The frequency of withdrawal movement in the group pretreated with thiopental was lower than in the control group (34 vs. 13, p < 0.05). We concluded that pretreatment with 2 mL (50 mg) thiopental is effective in reducing pain caused by the intravenous injection of rocuronium. PMID:16385651

A 2-year step-down withdrawal from inhaled corticosteroids in asthmatic children receiving immunotherapy.

PubMed

He, Chun-Hui; Li, Xing; Lin, Jun-Hong; Xiao, Qiang; Yu, Jia-Lu; Liu, Ying-Fen; Jiang, Wen-Hui; Chen, Chen; Deng, Li; Zhou, Jie

2017-12-01

Inhaled corticosteroids (ICSs) for treating asthma are controversial because of their negative effects on the growth of asthmatic children and without clearly defined withdrawal strategy. A 2-year ICS step-down and withdrawal strategy has been developed for asthmatic children receiving 3-year subcutaneous immunotherapy (SCIT). Eleven children were included into the SCIT group and 13 children into the ICS group. ICSs were discontinued when children met the following criteria: requiring only 1 puffper day, with good control, for at least 6 months; having a forced expiratory volume in 1 second (FEV 1 )/forced vital capacity ≥80%; and SCIT discontinued for ≥24 months. The main endpoints were the results of both the childhood asthma control test (C-CAT) and the methacholine bronchial provocation test. In the SCIT group, all the 11 children had ICS discontinued, with one child developed asthma attack after pneumonia and received ICS again after completion of SCIT. In the ICS group, five children discontinued ICS and developed asthma attacks later and received ICS again; the other eight children developed severe symptoms during ICS step-down. Thus, the discontinuation of ICS was only achieved in the SCIT group. The dose of methacholine that caused a decrease of 20% in FEV 1 continued to improve after discontinuation of ICS for the SCIT group and presented better results than the ICS group (P=0.050). After completion of SCIT, the C-CAT had improved significantly after 30 months of treatment compared with the ICS group (P<0.05). In the present study, we developed a 2-year step-down and withdrawal strategy from ICSs strategy for allergic asthma children receiving SCIT; the strategy was efficacious and safe.

Preparing Nursing and Social Work Students to Care for Patients in Acute Alcohol Withdrawal.

PubMed

Gates, Sharon A; Brown, James R

Alcohol and other drug abuse has become a national crisis with approximately 26% of general medical patients having alcohol-related problems. New nurses and social workers are often not prepared to care for patients with severe alcohol withdrawal symptoms because they lack experience in actual crisis situations. The purpose of this study was to prepare nursing and social work students to care for a patient undergoing an acute alcohol withdrawal process. Nine groups of 8-10 students participated in a 2.5-hour simulation event that included an alcohol withdrawal seizure, team meeting, and discharge of the patient. Students recognized the importance of all the professional roles and how each professional benefits patient care. Before the simulation, students thought they were prepared to care for patients experiencing alcohol withdrawal; however, the crisis of an alcohol seizure decreased the student's ability to perform skills and communicate effectively. These findings suggest that new nurses and social workers may not be prepared to care for the acute alcohol withdrawal patient.

Synthesis and Pharmacology of 1-Alkyl-3-(1-naphthoyl)indoles: Steric and Electronic Effects of 4- and 8-Halogenated Naphthoyl Substituents.

PubMed Central

Wiley, Jenny L.; Smith, Valerie J.; Chen, Jianhong; Martin, Billy R.; Huffman, John W.

2012-01-01

To develop SAR at both the cannabinoid CB1 and CB2 receptors for 3-(1-naphthoyl)indoles bearing moderately electron withdrawing substituents at C-4 of the naphthoyl moiety, 1-propyl and 1-pentyl-3-(4-fluoro, chloro, bromo and iodo-1-naphthoyl) derivatives were prepared. To study the steric and electronic effects of substituents at the 8-position of the naphthoyl group, the 3-(4-chloro, bromo and iodo-1-naphthoyl)indoles were also synthesized. The affinities of both groups of compounds for the CB1 and CB2 receptors were determined and several of them were evaluated in vivo in the mouse. The effects of these substituents on receptor affinities and in vivo activity are discussed and structure-activity relationships are presented. Although many of these compounds are selective for the CB2 receptor, only three JWH-423, 1-propyl-3-(4-iodo-1-naphthoyl)indole, JWH-422, 2-methyl-1-propyl-3-(4-iodo-1-naphthoyl)indole, the 2-methyl analog of JWH-423 and JWH-417, 1-pentyl-3-(8-iodo-1-naphthoyl)indole, possess the desirable combination of low CB1 affinity and good CB2 affinity. PMID:22341572

Reactivity of hydropersulfides toward the hydroxyl radical unraveled: disulfide bond cleavage, hydrogen atom transfer, and proton-coupled electron transfer.

PubMed

Anglada, Josep M; Crehuet, Ramon; Adhikari, Sarju; Francisco, Joseph S; Xia, Yu

2018-02-14

Hydropersulfides (RSSH) are highly reactive as nucleophiles and hydrogen atom transfer reagents. These chemical properties are believed to be key for them to act as antioxidants in cells. The reaction involving the radical species and the disulfide bond (S-S) in RSSH, a known redox-active group, however, has been scarcely studied, resulting in an incomplete understanding of the chemical nature of RSSH. We have performed a high-level theoretical investigation on the reactions of the hydroxyl radical (˙OH) toward a set of RSSH (R = -H, -CH 3 , -NH 2 , -C(O)OH, -CN, and -NO 2 ). The results show that S-S cleavage and H-atom abstraction are the two competing channels. The electron inductive effect of R induces selective ˙OH substitution at one sulfur atom upon S-S cleavage, forming RSOH and ˙SH for the electron donating groups (EDGs), whereas producing HSOH and ˙SR for the electron withdrawing groups (EWGs). The H-Atom abstraction by ˙OH follows a classical hydrogen atom transfer (hat) mechanism, producing RSS˙ and H 2 O. Surprisingly, a proton-coupled electron transfer (pcet) process also occurs for R being an EDG. Although for RSSH having EWGs hat is the leading channel, S-S cleavage can be competitive or even dominant for the EDGs. The overall reactivity of RSSH toward ˙OH attack is greatly enhanced with the presence of an EDG, with CH 3 SSH being the most reactive species found in this study (overall rate constant: 4.55 × 10 12 M -1 s -1 ). Our results highlight the complexity in RSSH reaction chemistry, the extent of which is closely modulated by the inductive effect of the substituents in the case of the oxidation by hydroxyl radicals.

Decision support during electronic prescription to stem antibiotic overuse for acute respiratory infections: a long-term, quasi-experimental study.

PubMed

Gifford, Jeneen; Vaeth, Elisabeth; Richards, Katherine; Siddiqui, Tariq; Gill, Christine; Wilson, Lucy; DeLisle, Sylvain

2017-07-31

Interventions to support decision-making can reduce inappropriate antibiotic use for acute respiratory infections (ARI), but they may not be sustainable. The objective of the study is to evaluate the long-term effectiveness of a clinical decision-support system (CDSS) interposed at the time of electronic (e-) prescriptions for selected antibiotics. This is a retrospective, observational intervention study, conducted within a large, statewide Veterans Affairs health system. Participants are outpatients with an initial visit for ARI. A CDSS was deployed upon e-prescription of selected antibiotics during the study period. From 01/2004 to 05/2006 (pre-withdrawal period), the CDSS targeted azithromycin and the fluoroquinolone gatifloxacin. From 05/2006 to 12/2011 (post-withdrawal period), the CDSS was retained for azithromycin but withdrawn for the fluoroquinolone. A manual record review was conducted to determine concordance of antibiotic prescription with ARI treatment guidelines. Of 1131 included ARI visits, 380 (33.6%) were guideline-concordant. For azithromycin, concordance did not change between the pre- and post-withdrawal periods, and adjusted odds of concordance was 8.8 for the full study period, compared to unrestricted antibiotics. For fluoroquinolones, guideline concordance decreased from 88.6% (39 of 44 visits) to 51.3% (59 of 115 visits), pre- vs. post-withdrawal periods (p < 0.005). The adjusted odds of concordance compared to "All Other Antibiotics" visits decreased from 24.4 (95% CI 9.0-66.3) pre-withdrawal to 5.5 (95% CI 3.5-8.8) post-withdrawal (p = .008). Concordance did not change between those same time periods for antibiotics that were never subjected to the intervention ("All Other Antibiotics"). A CDSS interposed at the time of e-prescription of selected antibiotics can shift their use toward ARI treatment guidelines, and this effect can be maintained over the long term as long as the CDSS remains in place. Removal of the CDSS after 3.5 years of implementation resulted in a rise in guideline-discordant antibiotic use.

Post-Marketing Regulation of Medicines Withdrawn from the Market Because of Drug-Attributed Deaths: An Analysis of Justification.

PubMed

Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

2017-05-01

Several medicinal products have been withdrawn from the market because of drug-attributed deaths. However, there has been no investigation of whether such withdrawals were justified, and the extent to which confirmatory studies are used to investigate drug-adverse event relationships when deaths are reported is uncertain. We documented medicinal products withdrawn from the market because of drug-attributed deaths, identified confirmatory studies investigating the drug-adverse event relationships, examined whether withdrawals of medicinal products because of drug-attributed deaths after marketing were justified based on a mechanistic analysis, and examined the trends over time. We searched electronic and non-electronic sources to identify medicinal products that were withdrawn because of drug-attributed deaths. We used a previously published algorithm to examine whether the withdrawals of products were justified. We then searched PubMed and Google Scholar to identify studies investigating the drug-adverse event relationships, used the Oxford Centre for Evidence-Based Medicine criteria to document the levels of evidence, and assessed whether the evidence of an association was confirmed. We included 83 medicinal products. The reasons for withdrawal appeared to have been justified in 80 cases (96%). The median interval between the first reported adverse reaction that was related to the cause of death and the first reported death was 1 year (interquartile range = 1-3); products were withdrawn sooner when the interval between the first reported relevant adverse reaction and the first death was shorter. Confirmatory studies were conducted in 57 instances (69%), and there was evidence of an association in 52 cases (63%). Four products (5%) were re-introduced after initial withdrawal. Regulatory authorities have been justified in making withdrawal decisions when deaths have been attributed to medicinal products, using the precautionary principle when alternative decisions could have been made. Medicinal products are likely to be quickly withdrawn from the market when there is a short interval to the first reported deaths. The use of an algorithm such as we have used in this study could help to expedite the process of decision making.

A lack of association between severity of nicotine withdrawal and individual differences in compensatory nicotine self-administration in rats

PubMed Central

Harris, Andrew C.; Pentel, Paul R.; Burroughs, Danielle; Staley, Mylissa D.; LeSage, Mark G.

2013-01-01

Rationale Compensatory smoking may represent an adverse consequence of smoking reduction or the use of reduced nicotine tobacco products. Factors contributing to individual variability in compensation are poorly understood. Objective To examine whether severity of nicotine withdrawal as measured by elevated intracranial self-stimulation (ICSS) thresholds is related to individual differences in compensatory nicotine self-administration (NSA) following unit dose reduction. Methods Rats were trained for ICSS and NSA (0.06 mg/kg/inf). After stabilization, effects of reducing the nicotine unit dose to 0.03 mg/kg/inf were examined. Following reacquisition of NSA (0.06 mg/kg/inf), effects of antagonist-precipitated withdrawal and saline extinction (spontaneous withdrawal) were examined. Results Reducing the NSA unit dose produced partial compensation as indicated by increased infusion rates but a 35% mean decrease in daily nicotine intake. Magnitude of compensation varied considerably among rats. Dose reduction did not elicit withdrawal in rats as a group, although there were substantial increases in ICSS thresholds in some animals. Intracranial self-stimulation thresholds were consistently elevated during precipitated and spontaneous withdrawal, confirming that rats were nicotine-dependent. Individual differences in compensation were not correlated with changes in ICSS thresholds during dose reduction, precipitated withdrawal, or spontaneous withdrawal. In a secondary analysis, greater precipitated withdrawal severity predicted greater initial nicotine-seeking during extinction. Conclusions Severity of nicotine withdrawal was not related to the degree of compensation in this protocol. These data do not support a role for nicotine withdrawal in individual differences in compensation during reduced nicotine exposure, but do suggest that withdrawal may contribute to nicotine-seeking during early abstinence. PMID:21494791

12 CFR 330.1 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... means a form of business in which one person owns all the assets of the business, in contrast to a..., payment orders of withdrawal, telephone or other electronic media transfers, or other similar items for...

12 CFR Part 745 - SHARE INSURANCE AND APPENDIX

Code of Federal Regulations, 2013 CFR

2013-01-01

..., payment orders of withdrawal, telephone or other electronic media transfers, or other similar items for... in good faith and in the regular course of business. (3) The account records of an insured credit...

12 CFR Part 745 - SHARE INSURANCE AND APPENDIX

Code of Federal Regulations, 2012 CFR

2012-01-01

..., payment orders of withdrawal, telephone or other electronic media transfers, or other similar items for... in good faith and in the regular course of business. (3) The account records of an insured credit...

Oral Finasteride Presents With Sexual-Unrelated Withdrawal in Long-Term Treated Androgenic Alopecia in Men.

PubMed

Perez-Mora, Nicolas; Velasco, Carlos; Bermüdez, Fernando

2015-01-01

Side effects associated with oral finasteride (FT) (1 mg/d) and topical 5% minoxidil (M5) have been previously described. The authors have evaluated long-term adverse effects and causes of long-term therapy withdrawal in patients with androgenic alopecia (AGA) treated with M5+FT vs M5 without FT. A total of 130 AGA patients with a minimum 2-year follow-up volunteered to complete a questionnaire on side effects. Patients' responses were classified as "never," "rarely," "sometimes," "often," and "all the time." An adverse effect was considered in the presence of an "often" or "all the time" response. A total of 100 patients received combined M5+FT and were compared with 30 patients receiving single-therapy M5 according to the physician's clinical criteria. Erectile dysfunction (3%), diminished libido (4%), and reduced ejaculation (7%) were present in patients taking M5+FT but were absent in patients taking M5. Only 1 of 100 patients taking M5+FT quit long-term therapy due to sexual adverse effects (diminished libido). The main causes for therapy withdrawal in the FT group were lack of positive results in 11% and in the M5 group side effects in 4% (P < .02). Increased body hair was different between groups: with 6.6% in the M5 group and 4% in the M5+FT group (P < .03). FT demonstrates sexual-unrelated reasons as the main cause of therapy withdrawal in long-term treated AGA patients.

Withdrawal of long-term epoprostenol therapy in pulmonary arterial hypertension (PAH).

PubMed

Calcaianu, George; Calcaianu, Mihaela; Canuet, Matthieu; Enache, Irina; Kessler, Romain

2017-01-01

Once initiated for pulmonary arterial hypertension (PAH), epoprostenol treatment usually needs to be delivered for an indefinite duration. It is possible that some participants could be transitioned from epoprostenol to oral therapies. We retrospectively evaluated eight PAH participants transitioned from epoprostenol to PAH oral drugs. The criteria for epoprostenol withdrawal were: (1) persistent improvement of clinic and hemodynamic status; (2) stable dose of epoprostenol for the last three months; and (3) the participant's preference for oral therapy after evaluation of risk-benefit. We evaluated the clinical, functional, and hemodynamic status at baseline, at withdrawal, and after the transition to oral PAH therapy. The transition was completed in all eight participants. Four participants had a complete successful transition (CT) with a stable clinical and hemodynamic course and four participants had a partial successful transition (PT) remaining stable clinically, with a mild hemodynamic worsening, but without need to re-initiate epoprostenol therapy. The four CT participants were treated with epoprostenol for a shorter period of time (CT group: 35 ± 30 versus PT group: 79 ± 49 months, P = 0.08). Mean epoprostenol dosage was lower in the CT group (CT group: 15 ± 1.5 ng/kg/min versus PT group: 24 ± 11 ng/kg/min, P = 0.09). Safe withdrawal of epoprostenol treatment and transition to oral PAH therapy was possible in a small and highly selected group of participants. The majority of these participants had a porto-pulmonary PAH or PAH associated to HIV infection.

Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain, kidney and liver oxidative stress and some biochemical parameters in male rats.

PubMed

Ragy, Merhan Mamdouh

2015-01-01

Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1 h/d for 60 d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1 h/d for 60 d then left for 30 d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levels in brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p < 0.05), while serum catecholamines were insignificantly higher in the exposed rats. These alterations were corrected by withdrawal. In conclusion, electromagnetic field emitting from mobile phone might produce impairments in some biochemicals changes and oxidative stress in brain, liver and renal tissue of albino rats. These alterations were corrected by withdrawal.

Theoretical investigations of molecular wires: Electronic spectra and electron transport

NASA Astrophysics Data System (ADS)

Palma, Julio Leopoldo

The results of theoretical and computational research are presented for two promising molecular wires, the Nanostar dendrimer, and a series of substituted azobenzene derivatives connected to aluminum electrodes. The electronic absorption spectra of the Nanostar (a phenylene-ethynylene dendrimer attached to an ethynylperylene chromophore) were calculated using a sequential Molecular Dynamics/Quantum Mechanics (MD/QM) method to perform an analysis of the temperature dependence of the electronic absorption process. We modeled the Nanostar as a series of connected units, and performed MD simulations for each chromophore at 10 K and 300 K to study how the temperature affected the structures and, consequently, the spectra. The absorption spectra of the Nanostar were computed using an ensemble of 8000 structures for each chromophore. Quantum Mechanical (QM) ZINDO/S calculations were performed for each conformation in the ensemble, including 16 excited states, for a total of 128,000 excitation energies. The spectral intensity was then scaled linearly with the number of conjugated units. Our calculations for both the individual chromophores and the Nanostar, are in good agreement with experiments. We explain in detail the effects of temperature and the consequences for the absorption process. The second part of this thesis presents a study of the effects of chemical substituents on the electron transport properties of the azobenzene molecule, which has been proposed recently as a component of a light-driven molecular switch. This molecule has two stable conformations (cis and trans) in its electronic ground state, with considerable differences in their conductance. The electron transport properties were calculated using first-principles methods combining non-equilibrium Green's function (NEGF) techniques with density functional theory (DFT). For the azobenzene studies, we included electron-donating groups and electron-withdrawing groups in meta- and ortho-positions with respect to the azo group. The results showed that the molecular structure is crucial in optimizing the electron transport properties of chemical structures, and that the transport properties in electronic devices at the molecular level can be manipulated, enhanced or suppressed by a careful consideration of the effects of chemical modification.

Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms.

PubMed

Tsertsvadze, Alexander; Yazdi, Fatemeh; Fink, Howard A; MacDonald, Roderick; Wilt, Timothy J; Bella, Anthony J; Ansari, Mohammed T; Garritty, Chantelle; Soares-Weiser, Karla; Daniel, Raymond; Sampson, Margaret; Moher, David

2009-10-01

To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.

Colorimetric detection of anions in aqueous media using N-monosubstituted diaminomaleonitrile-based azo-azomethine receptors: Real-life applications

NASA Astrophysics Data System (ADS)

Khanmohammadi, Hamid; Rezaeian, Khatereh; Abdollahi, Alieh

2015-03-01

New N-monosubstituted diaminomaleonitrile-based azo-azomethine dyes have been synthesized in order to develop colorimetric sensors for detection of biologically important anions in aqueous media. Importantly, the reported sensor decorated with strong electron-withdrawing group can detect inorganic fluoride in water even at 0.037 ppm level, which is lower than WHO permissible level (below 1 ppm). Successfully, the prepared dyes were used for qualitative and quantitative detection of inorganic fluoride in toothpaste and mouthwash. The anion recognition mechanism was also investigated by detailed UV-Vis and 1H NMR experiments. The detailed 1H NMR experiments corroborated that anion recognition is based on the deprotonation phenomenon.

Identification of fungal ene-reductase activity by means of a functional screening.

PubMed

Romagnolo, Alice; Spina, Federica; Brenna, Elisabetta; Crotti, Michele; Parmeggiani, Fabio; Varese, Giovanna Cristina

2015-06-01

Bioeconomy stresses the need of green processes promoting the development of new methods for biocatalyzed alkene reductions. A functional screening of 28 fungi belonging to Ascomycota, Basidiomycota, and Zygomycota isolated from different habitats was performed to analyze their capability to reduce C=C double bonds towards three substrates (cyclohexenone, α-methylnitrostyrene, and α-methylcinnamaldehyde) with different electron-withdrawing groups, i.e., ketone, nitro, and aldehyde, respectively. Almost all the fungi showed this reducing activity. Noteworthy Gliomastix masseei, Mucor circinelloides, and Mucor plumbeus resulted versatile and effective, being able to reduce all the model substrates quickly and with high yields. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skarzewski, J.; Aoki, M.; Sekiquchi, S.

The alkaline hydrolyses of anilides have been studied extensively, but those of anilides bearing ortho substituents seem to be a rather unexplored field. As was shown for p-nitroacetanilide (1), the reaction mechanism of the base-catalyzed hydrolyses of anilides with strongly electron-withdrawing substituents on the phenyl moiety differs somewhat from the general one. The difference is caused by higher acidity of leaving-group nitroanilines. The results obtained in the case of the alkaline hydrolysis of N-ethyl-2,4-dinitroacetanilide are expected to conform to the reaction mechanism proposed for all other anilides, but the rate-determining step may change for such sterically hindered derivatives. That thismore » prediction is fulfilled will be developed in latter sections.« less

Conformations and charge distributions of diazocyclopropanes

NASA Astrophysics Data System (ADS)

Borges, Itamar, Jr.

Three diazo-substituted cyclopropane compounds, which have been suggested as new potential high energy compounds, were studied employing the B3LYP-DFT/6-31G(d,p) method. Geometries were optimized. Distributed multipole analysis, computed from the B3LYP-DFT/6-31G(d,p) density matrix, was used to describe the details of the molecular charge distribution of the three molecules. It was verified that electron withdrawing from the C ring atoms and charge build-up on the N atoms bonded to the ring increased with the number of diazo groups. These effects were related to increased sensitivity to impact and easiness of C bond N bond breaking in the three compounds.

Cerebrolysin Attenuates Heat Shock Protein (HSP 72 KD) Expression in the Rat Spinal Cord Following Morphine Dependence and Withdrawal: Possible New Therapy for Pain Management

PubMed Central

Sharma, Hari S; Ali, Syed F; Patnaik, Ranjana; Zimmermann-Meinzingen, Sibilla; Sharma, Aruna; Muresanu, Dafin F

2011-01-01

The possibility that pain perception and processing in the CNS results in cellular stress and may influence heat shock protein (HSP) expression was examined in a rat model of morphine dependence and withdrawal. Since activation of pain pathways result in exhaustion of growth factors, we examined the influence of cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,) on morphine induced HSP expression. Rats were administered morphine (10 mg/kg, s.c. /day) for 12 days and the spontaneous withdrawal symptoms were developed by cessation of the drug administration on day 13th that were prominent on day 14th and continued up to day 15th (24 to 72 h periods). In a separate group of rats, cerebrolysin was infused intravenously (5 ml/kg) once daily from day one until day 15th. In these animals, morphine dependence and withdrawal along with HSP immunoreactivity was examined using standard protocol. In untreated group mild HSP immunoreaction was observed during morphine tolerance, whereas massive upregulation of HSP was seen in CNS during withdrawal phase that correlated well with the withdrawal symptoms and neuronal damage. Pretreatment with cerebrolysin did not affect morphine tolerance but reduced the HSP expression during this phase. Furthermore, cerebrolysin reduced the withdrawal symptoms on day 14th to 15th. Taken together these observations suggest that cellular stress plays an important role in morphine induced pain pathology and exogenous supplement of growth factors, i.e. cerebrolysin attenuates HSP expression in the CNS and induce neuroprotection. This indicates a new therapeutic role of cerebrolysin in the pathophysiology of drugs of abuse, not reported earlier. PMID:21886595

Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR?

PubMed

Kelly, Meredith A; Pavlicova, Martina; Glass, Andrew; Mariani, John J; Bisaga, Adam; Sullivan, Maria A; Nunes, Edward V; Levin, Frances R

2014-11-01

Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group. We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR=51, Placebo=52). Marijuana use was dichotomized into smoking (THC>100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis. The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7-9, even when controlling for MWC scores (week 7 Risk Difference (RD)=0.11, p=0.034; week 8 RD=0.20, p=0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD=0.03, p=0.380; week 11 RD=0.07, p=0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models. Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR?

PubMed Central

Kelly, Meredith A.; Pavlicova, Martina; Glass, Andrew; Mariani, John J.; Bisaga, Adam; Sullivan, Maria A.; Nunes, Edward V.; Levin, Frances R.

2014-01-01

Background and aims Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group. Methods We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR = 51, Placebo = 52). Marijuana use was dichotomized into smoking (THC > 100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis. Results The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7–9, even when controlling for MWC scores (week 7 Risk Difference (RD) = 0.11, p = 0.034; week 8 RD = 0.20, p = 0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD = 0.03, p = 0.380; week 11 RD = 0.07, p = 0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models. Conclusions Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use. PMID:25283697

Pathological characteristics of liver allografts from donation after brain death followed by cardiac death in pigs.

PubMed

Ye, Hui; Wang, Dong-Ping; Zhang, Chuan-Zhao; Zhang, Long-Juan; Wang, Hao-Chen; Li, Zhuo-Hui; Chen, Zhen; Zhang, Tao; Cai, Chang-Jie; Ju, Wei-Qiang; Ma, Yi; Guo, Zhi-Yong; He, Xiao-Shun

2014-10-01

Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P<0.05). And there was no significant difference between DBD group and DBCD group (P>0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

Molecular design of photovoltaic materials for polymer solar cells: toward suitable electronic energy levels and broad absorption.

PubMed

Li, Yongfang

2012-05-15

Bulk heterojunction (BHJ) polymer solar cells (PSCs) sandwich a blend layer of conjugated polymer donor and fullerene derivative acceptor between a transparent ITO positive electrode and a low work function metal negative electrode. In comparison with traditional inorganic semiconductor solar cells, PSCs offer a simpler device structure, easier fabrication, lower cost, and lighter weight, and these structures can be fabricated into flexible devices. But currently the power conversion efficiency (PCE) of the PSCs is not sufficient for future commercialization. The polymer donors and fullerene derivative acceptors are the key photovoltaic materials that will need to be optimized for high-performance PSCs. In this Account, I discuss the basic requirements and scientific issues in the molecular design of high efficiency photovoltaic molecules. I also summarize recent progress in electronic energy level engineering and absorption spectral broadening of the donor and acceptor photovoltaic materials by my research group and others. For high-efficiency conjugated polymer donors, key requirements are a narrower energy bandgap (E(g)) and broad absorption, relatively lower-lying HOMO (the highest occupied molecular orbital) level, and higher hole mobility. There are three strategies to meet these requirements: D-A copolymerization for narrower E(g) and lower-lying HOMO, substitution with electron-withdrawing groups for lower-lying HOMO, and two-dimensional conjugation for broad absorption and higher hole mobility. Moreover, better main chain planarity and less side chain steric hindrance could strengthen π-π stacking and increase hole mobility. Furthermore, the molecular weight of the polymers also influences their photovoltaic performance. To produce high efficiency photovoltaic polymers, researchers should attempt to increase molecular weight while maintaining solubility. High-efficiency D-A copolymers have been obtained by using benzodithiophene (BDT), dithienosilole (DTS), or indacenodithiophene (IDT) donor unit and benzothiadiazole (BT), thienopyrrole-dione (TPD), or thiazolothiazole (TTz) acceptor units. The BDT unit with two thienyl conjugated side chains is a highly promising unit in constructing high-efficiency copolymer donor materials. The electron-withdrawing groups of ester, ketone, fluorine, or sulfonyl can effectively tune the HOMO energy levels downward. To improve the performance of fullerene derivative acceptors, researchers will need to strengthen absorption in the visible spectrum, upshift the LUMO (the lowest unoccupied molecular orbital) energy level, and increase the electron mobility. [6,6]-Phenyl-C(71)-butyric acid methyl ester (PC(70)BM) is superior to [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) because C(70) absorbs visible light more efficiently. Indene-C(60) bisadduct (ICBA) and Indene-C(70) bisadduct (IC(70)BA) show 0.17 and 0.19 eV higher LUMO energy levels, respectively, than PCBM, due to the electron-rich character of indene and the effect of bisadduct. ICBA and IC(70)BA are excellent acceptors for the P3HT-based PSCs.

19 CFR 122.78 - Entry or withdrawal for exportation or for transportation and exportation.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart; Electronic Manifest Requirements for Passengers, Crew Members, and Non...

Psychiatric aspects of acute withdrawal from gamma-hydroxybutyrate (GHB) and its analogue gamma-butyrolactone (GBL): implications for psychiatry services in the general hospital.

PubMed

Choudhuri, Debajeet; Cross, Sean; Dargan, Paul I; Wood, David M; Ranjith, Gopinath

2013-06-01

The objective of this study was to describe the psychiatric symptoms, management and outcomes in a consecutive series of patients being managed medically for symptoms of withdrawal from gamma-hydroxybutyrate (GHB) and its analogue gamma-butyrolactone (GBL) in a general hospital setting. A toxicology database was used to identify patients presenting with a history suggestive of withdrawal from GHB and analogues. Electronic and paper medical records were searched for demographic features, neuropsychiatric symptoms, psychiatric management while in hospital and overall outcome. There were 31 presentations with withdrawal from the drugs involving 20 patients. Of these 17 (54%) were referred to and seen by the liaison psychiatry team. Anxiety (61.3%) and agitation (48.4%) were the most common symptoms. Of the 17 cases seen by the liaison psychiatry team, 52.9% required close constant observation by a mental health nurse and 29.4% required to be detained in hospital under mental health legislation. The significant proportion of patients presenting with neuropsychiatric symptoms and requiring intensive input from the liaison psychiatry team during withdrawal from GHB and its analogues points to the importance of close liaison between medical and psychiatric teams in managing these patients in the general hospital.

Narp regulates long-term aversive effects of morphine withdrawal.

PubMed

Reti, Irving M; Crombag, Hans S; Takamiya, Kogo; Sutton, Jeffrey M; Guo, Ning; Dinenna, Megan L; Huganir, Richard L; Holland, Peter C; Baraban, Jay M

2008-08-01

Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. Because Narp is an immediate early gene product that is secreted at synaptic sites and binds to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, the authors found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, the authors evaluate whether long-term aversive effects of morphine withdrawal are altered in Narp knockout (KO) mice. The authors found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than do wild type (WT) controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction.

The Different Sensitive Behaviors of a Hydrogen-Bond Acidic Polymer-Coated SAW Sensor for Chemical Warfare Agents and Their Simulants

PubMed Central

Long, Yin; Wang, Yang; Du, Xiaosong; Cheng, Luhua; Wu, Penglin; Jiang, Yadong

2015-01-01

A linear hydrogen-bond acidic (HBA) linear functionalized polymer (PLF), was deposited onto a bare surface acoustic wave (SAW) device to fabricate a chemical sensor. Real-time responses of the sensor to a series of compounds including sarin (GB), dimethyl methylphosphonate (DMMP), mustard gas (HD), chloroethyl ethyl sulphide (2-CEES), 1,5-dichloropentane (DCP) and some organic solvents were studied. The results show that the sensor is highly sensitive to GB and DMMP, and has low sensitivity to HD and DCP, as expected. However, the sensor possesses an unexpected high sensitivity toward 2-CEES. This good sensing performance can’t be solely or mainly attributed to the dipole-dipole interaction since the sensor is not sensitive to some high polarity solvents. We believe the lone pair electrons around the sulphur atom of 2-CEES provide an electron-rich site, which facilitates the formation of hydrogen bonding between PLF and 2-CEES. On the contrary, the electron cloud on the sulphur atom of the HD molecule is offset or depleted by its two neighbouring strong electron-withdrawing groups, hence, hydrogen bonding can hardly be formed. PMID:26225975

Update to the Ground-Water Withdrawals Database for the Death Valley Regional Ground-Water Flow System, Nevada and California, 1913-2003

USGS Publications Warehouse

Moreo, Michael T.; Justet, Leigh

2008-01-01

Ground-water withdrawal estimates from 1913 through 2003 for the Death Valley regional ground-water flow system are compiled in an electronic database to support a regional, three-dimensional, transient ground-water flow model. This database updates a previously published database that compiled estimates of ground-water withdrawals for 1913-1998. The same methodology is used to construct each database. Primary differences between the 2 databases are an additional 5 years of ground-water withdrawal data, well locations in the updated database are restricted to Death Valley regional ground-water flow system model boundary, and application rates are from 0 to 1.5 feet per year lower than original estimates. The lower application rates result from revised estimates of crop consumptive use, which are based on updated estimates of potential evapotranspiration. In 2003, about 55,700 acre-feet of ground water was pumped in the DVRFS, of which 69 percent was used for irrigation, 13 percent for domestic, and 18 percent for public supply, commercial, and mining activities.

Response to CPAP Withdrawal in Patients with Mild Versus Severe Obstructive Sleep Apnea/Hypopnea Syndrome

PubMed Central

Young, Laura R.; Taxin, Zachary H.; Norman, Robert G.; Walsleben, Joyce A.; Rapoport, David M.; Ayappa, Indu

2013-01-01

Background: Patients with obstructive sleep apnea/hypopnea syndrome (OSAHS), even those generally compliant with CPAP therapy, often intermittently discontinue CPAP. Study Objective: Examine the impact of CPAP withdrawal on sleep, sleep disordered breathing (SDB), and daytime function in subjects with varying severity of OSAHS. Patients and Interventions: Forty-two subjects (26M/16 F) with OSAHS (AHI4% = 45.2 ± 35.5/h pretreatment) on CPAP for 4 months were evaluated on the second night of CPAP withdrawal. Sleep architecture, SDB indices, and subjective/objective daytime function were assessed pretreatment, on CPAP therapy, and after CPAP withdrawal. Comparisons were made between pretreatment and CPAP withdrawal for the entire group, and for subgroups of mild/moderate (AHI4% < 30/h, n = 22) and severe (AHI4% > 30/h, n = 20) SDB. Results: Overall, and for mild/moderate subjects, SDB indices returned to pretreatment values on CPAP withdrawal but with fewer apneas and more hypopneas/RERAs. For severe SDB, the event frequency (AI, AHI4%, and RDI) was lower and O2 desaturation was improved on CPAP withdrawal. Across SDB severity, sleep architecture showed lower %REM (15.6% vs 12.9%, P = 0.009) on the CPAP withdrawal compared to pretreatment. Stanford Sleepiness Score, MSLT, and PVT measures were not significantly different between pretreatment and CPAP withdrawal. Conclusions: Over a wide range of SDB severity CPAP withdrawal results in recurrence of SDB, albeit with less severe O2 desaturation. Subjective/objective daytime function returned to pretreatment levels. Sleep architecture changes on CPAP withdrawal (acute SDB) may reflect reduced sleep pressure compared to pretreatment chronic SDB. Our data suggest detrimental effects of even brief withdrawal of CPAP in subjects with both mild and severe OSAHS. Citation: Young LR; Taxin ZH; Norman RG; Walsleben JA; Rapoport DM; Ayappa I. Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome. SLEEP 2013;36(3):405-412. PMID:23449493

Comparison of the effects of the uncompetitive N-methyl-D-aspartate antagonist (+-)-5-aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (ADCI) with its structural analogs dizocilpine (MK-801) and carbamazepine on ethanol withdrawal seizures.

PubMed

Grant, K A; Snell, L D; Rogawski, M A; Thurkauf, A; Tabakoff, B

1992-03-01

The ability of [(+-)-5-aminocarbonyl-10,11-dihydro-5H-di-benzo [a,d]cyclohepten-5,10-imine (ADCI) and its structural analogs dizocilipine (MK-801) and carbamazepine to block ethanol withdrawal seizures was tested in mice made physically dependent upon ethanol. Three injections of either ADCI (ranging from 1.0-10.0 mg/kg), dizocilpine (ranging from 0.1-1.0 mg/kg) or carbamazepine (ranging from 17-50 mg/kg) were administered during the first 7 hr of ethanol withdrawal. The severity of ethanol withdrawal seizures was rated during the first 11 hr of withdrawal and again at 24 hr after withdrawal of ethanol. ADCI and dizocilpine suppressed the severity and occurrence of the withdrawal seizures in a dose-dependent fashion, whereas carbamazepine was ineffective in blocking the withdrawal seizures. The relative potencies of dizocilpine, ADCI and carbamazepine in suppressing ethanol withdrawal seizures corresponded with the relative potencies of the compounds in displacing [3H]dizocilpine from mouse cortical membrane preparations. These findings are consistent with the suggestion that blockade of N-methyl-D-aspartate-mediated neurotransmission is an effective treatment for decreasing ethanol withdrawal seizures. ADCI also blocked the occurrence of withdrawal-associated whole body tremors, whereas dizocilpine and carbamazepine were ineffective in blocking the tremors. The doses of ADCI, dizocilpine and carbamazepine that resulted in motor incoordination on an accelerating rotarod task were determined in groups of naive mice. Dizocilpine in doses as low as 0.3 mg/kg produced a decreased ability to remain on the rotarod, whereas ADCI up to 30 mg/kg did not affect rotarod performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Photoswitching Behavior of 5-Phenylazopyrimidines: In Situ Irradiation NMR and Optical Spectroscopy Combined with Theoretical Methods.

PubMed

Čechová, Lucie; Kind, Jonas; Dračínský, Martin; Filo, Juraj; Janeba, Zlatko; Thiele, Christina M; Cigáň, Marek; Procházková, Eliška

2018-05-11

The photoswitching behavior of 5-phenylazopyrimidines was investigated by optical methods and NMR spectroscopy with in situ irradiation sustained by mathematical modeling and DFT calculations. Irradiation of various compounds with electron-donating groups on the pyrimidine ring and substituents with electron-withdrawing as well as electron-donating substituent in the para-position of the phenyl ring were examined. All compounds could be successfully converted to the cis isomer; this isomerization and the subsequent thermal fading were studied. Switching cycles can be repeated without signs of photodegradation for most of the compounds, which makes them adept to molecular photoswitches. Interestingly, the chloro and cyano derivatives can be switched without UV light, which makes them vis(π → π*)-vis(n → π*) photoswitches. Surprisingly equal trans-to- cis photoisomerization quantum yields for π → π* and n → π* excitation indicate the blocking of the inversion pathway following π → π* excitation. In contrast to that, DFT computations suggest the inversion mechanism for the reverse thermal cis-to- trans isomerization of 5-phenylazopyrimidines.

Assessing colonoscopic inspection skill using a virtual withdrawal simulation: a preliminary validation of performance metrics.

PubMed

Zupanc, Christine M; Wallis, Guy M; Hill, Andrew; Burgess-Limerick, Robin; Riek, Stephan; Plooy, Annaliese M; Horswill, Mark S; Watson, Marcus O; de Visser, Hans; Conlan, David; Hewett, David G

2017-07-12

The effectiveness of colonoscopy for diagnosing and preventing colon cancer is largely dependent on the ability of endoscopists to fully inspect the colonic mucosa, which they achieve primarily through skilled manipulation of the colonoscope during withdrawal. Performance assessment during live procedures is problematic. However, a virtual withdrawal simulation can help identify and parameterise actions linked to successful inspection, and offer standardised assessments for trainees. Eleven experienced endoscopists and 18 endoscopy novices (medical students) completed a mucosal inspection task during three simulated colonoscopic withdrawals. The two groups were compared on 10 performance metrics to preliminarily assess the validity of these measures to describe inspection quality. Four metrics were related to aspects of polyp detection: percentage of polyp markers found; number of polyp markers found per minute; percentage of the mucosal surface illuminated by the colonoscope (≥0.5 s); and percentage of polyp markers illuminated (≥2.5 s) but not identified. A further six metrics described the movement of the colonoscope: withdrawal time; linear distance travelled by the colonoscope tip; total distance travelled by the colonoscope tip; and distance travelled by the colonoscope tip due to movement of the up/down angulation control, movement of the left/right angulation control, and axial shaft rotation. Statistically significant experienced-novice differences were found for 8 of the 10 performance metrics (p's < .005). Compared with novices, experienced endoscopists inspected more of the mucosa and detected more polyp markers, at a faster rate. Despite completing the withdrawals more quickly than the novices, the experienced endoscopists also moved the colonoscope more in terms of linear distance travelled and overall tip movement, with greater use of both the up/down angulation control and axial shaft rotation. However, the groups did not differ in the number of polyp markers visible on the monitor but not identified, or movement of the left/right angulation control. All metrics that yielded significant group differences had adequate to excellent internal consistency reliability (α = .79 to .90). These systematic differences confirm the potential of the simulated withdrawal task for evaluating inspection skills and strategies. It may be useful for training, and assessment of trainee competence.

An electro-optical and electron injection study of benzothiazole-based squaraine dyes as efficient dye-sensitized solar cell materials: a first principles study.

PubMed

Al-Fahdan, Najat Saeed; Asiri, Abdullah M; Irfan, Ahmad; Basaif, Salem A; El-Shishtawy, Reda M

2014-12-01

Squaraine dyes have attracted significant attention in many areas of daily life from biomedical imaging to semiconducting materials. Moreover, these dyes are used as photoactive materials in the field of solar cells. In the present study, we investigated the structural, electronic, photophysical, and charge transport properties of six benzothiazole-based squaraine dyes (Cis-SQ1-Cis-SQ3 and Trans-SQ1-Trans-SQ3). The effect of electron donating (-OCH3) and electron withdrawing (-COOH) groups was investigated intensively. Ground state geometry and frequency calculations were performed by applying density functional theory (DFT) at B3LYP/6-31G** level of theory. Absorption spectra were computed in chloroform at the time-dependent DFT/B3LYP/6-31G** level of theory. The driving force of electron injection (ΔG (inject)), relative driving force of electron injection (ΔG r (inject)), electronic coupling constants (|VRP|) and light harvesting efficiency (LHE) of all six compounds were calculated and compared with previously studied sensitizers. The ΔG (inject), ΔG r (inject) and |VRP| of all six compounds revealed that these sensitizers would be efficient dye-sensitized solar cell materials. Cis/Trans-SQ3 exhibited superior LHE as compared to other derivatives. The Cis/Trans geometric effect was studied and discussed with regard to electro-optical and charge transport properties.

Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

PubMed

Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

2015-05-05

Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. Copyright © 2015 Elsevier B.V. All rights reserved.

Occurrence and removal of pharmaceuticals, hormones, personal care products, and endocrine disrupters in a full-scale water reclamation plant.

PubMed

Tran, Ngoc Han; Gin, Karina Yew-Hoong

2017-12-01

This study provided the first comprehensive data on the occurrence and removal of twenty-five target emerging contaminants (ECs) in a full-scale water reclamation plant (WRP) in the Southeast Asian region. Nineteen out of the twenty-five ECs were ubiquitously detected in raw influent samples. Concentrations of the detected ECs in raw influent samples ranged substantially from 44.3 to 124,966ng/L, depending upon the compound and sampling date. The elimination of ECs in full-scale conventional activated sludge (CAS) and membrane bioreactor (MBR) systems at a local WRP was evaluated and compared. Several ECs, such as acetaminophen, atenolol, fenoprofen, indomethacin, ibuprofen, and oxybenzone, exhibited excellent removal efficiencies (>90%) in biological wastewater treatment processes, while some of the investigated compounds (carbamazepine, crotamiton, diclofenac, and iopamidol) appeared to be persistent in the both CAS and MBR systems. Field-based monitoring results showed that MBR outperformed CAS in the elimination of most target ECs. The relationship between molecular characteristics of ECs (i.e. physicochemical properties and structural features) and their removal efficiencies during biological wastewater treatment was also elucidated. Excellent removal efficiencies (>90%) were often noted for ECs with the sole presence of electron donating groups (i.e. phenolic [OH], amine [NH 2 ], methoxy [OCH 3 ], phenoxy [OC 6 H 5 ], or alkyl groups). Conversely, ECs with the absence of electron donating groups or the predominance of strong electron withdrawing groups (e.g. halogenated, carbonyl, carboxyl, and sulfonamide) tended to show poor removal efficiencies (<30%) in biological wastewater treatment processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlling the directionality of charge transfer in phthalocyaninato zinc sensitizer for a dye-sensitized solar cell: density functional theory studies.

PubMed

Wan, Liang; Qi, Dongdong; Zhang, Yuexing; Jiang, Jianzhuang

2011-01-28

Density functional theory (DFT) calculation on the molecular structures, charge distribution, molecular orbitals, electronic absorption spectra of a series of eight unsymmetrical phthalocyaninato zinc complexes with one peripheral (E)-2-cyano-3-(5-vinylthiophen-2-yl) acrylic acid substituent at 2 or 3 position as an electron-withdrawing group and a different number of electron-donating amino groups at the remaining peripheral positions (9, 10, 16, 17, 23, 24) of the phthalocyanine ring, namely ZnPc-β-A, ZnPc-β-A-I-NH(2), ZnPc-β-A-II-NH(2), ZnPc-β-A-III-NH(2), ZnPc-β-A-I,II-NH(2), ZnPc-β-A-I,III-NH(2), ZnPc-β-A-II,III-NH(2), and ZnPc-β-A-I,II,III-NH(2), reveals the effects of amino groups on the charge transfer properties of these phthalocyanine derivatives with a typical D-π-A electronic structure. The introduction of amino groups was revealed altering of the atomic charge distribution, lifting the frontier molecular orbital level, red-shift of the near-IR bands in the electronic absorption spectra, and finally resulting in enhanced charge transfer directionality for the phthalocyanine compounds. Along with the increase of the peripheral amino groups at the phthalocyanine ring from 0, 2, 4, to 6, the dihedral angle between the phthalocyanine ring and the average plane of the (E)-2-cyano-3-(5-vinylthiophen-2-yl) acrylic acid substituent increases from 0 to 3.3° in an irregular manner. This is in good contrast to the regular and significant change in the charge distribution, destabilization of frontier orbital energies, and red shift of near-IR bands of phthalocyanine compounds along the same order. In addition, comparative studies indicate the smaller effect of incorporating two amino groups onto the 16 and 17 than on 9 and 10 or 23 and 24 peripheral positions of the phthalocyanine ring onto the aforementioned electronic properties, suggesting the least effect on tuning the charge transfer property of the phthalocyanine compound via introducing two electron-donating amino groups onto the 16 and 17 peripheral positions. As expected, compound ZnPc-β-A-I,III-NH(2) with four amino groups at 9, 10, 23, and 24 positions of the phthalocyanine ring shows the best charge transfer directionality among the three phthalocyaninato zinc complexes with four peripheral amino groups.

THE EFFECTS OF DRONABINOL DURING DETOXIFICATION AND THE INITIATION OF TREATMENT WITH EXTENDED RELEASE NALTREXONE

PubMed Central

Bisaga, Adam; Sullivan, Maria A.; Glass, Andrew; Mishlen, Kaitlyn; Pavlicova, Martina; Haney, Margaret; Raby, Wilfrid N.; Levin, Frances R.; Carpenter, Kenneth M.; Mariani, John J.; Nunes, Edward V.

2015-01-01

Background Evidence suggests that the cannabinoid system is involved in the maintenance of opioid dependence. We examined whether dronabinol, a cannabinoid receptor type 1 partial agonist, reduces opioid withdrawal and increases retention in treatment with extended release naltrexone (XR-naltrexone). Methods Opioid dependent participants were randomized to receive dronabinol 30 mg/d (n=40) or placebo (n=20), under double-blind conditions, while they underwent inpatient detoxification and naltrexone induction. Before discharge all participants received an injection of XR-naltrexone, with an additional dose given four weeks later. Dronabinol or placebo was given while inpatient and for 5 weeks afterwards. The primary outcomes were the severity of opioid withdrawal, measured with the Subjective Opioid Withdrawal Scale, and retention in treatment at the end of the inpatient phase and at the end of the 8-week trial. Results The severity of opioid withdrawal during inpatient phase was lower in the dronabinol group relative to placebo group (p=0.006). Rates of successful induction onto XR-naltrexone (dronabinol 66%, placebo 55%) and completion of treatment (dronabinol 35%, placebo 35%) were not significantly different. Post-hoc analysis showed that the 32% of participants who smoked marijuana regularly during the outpatient phase had significantly lower ratings of insomnia and anxiety and were more likely to complete the 8-week trial. Conclusion Dronabinol reduced the severity of opiate withdrawal during acute detoxification but had no effect on rates of XR-naltrexone treatment induction and retention. Participants who elected to smoke marijuana during the trial were more likely to complete treatment regardless of treatment group assignment. PMID:26187456

Effects of withdrawal of phenytoin on cognitive and psychomotor functions in hospitalized epileptic patients on polytherapy.

PubMed

May, T W; Bulmahn, A; Wohlhüter, M; Rambeck, B

1992-08-01

The effects of the withdrawal of phenytoin (PT) on cognitive and psychomotor functions of long-term patients in an epilepsy centre were studied. The patients had been treated for many years (31.1 +/- 10.8 yrs.) with PT in combination with other antiepileptic drugs. The serum concentration of PT was in the lower to middle therapeutic range (6.8 +/- 3.1 mg/l). Only patients in which the efficacy of PT was questionable were included in the study. PT was withdrawn in 17 patients. The PT dose was not changed in 12 patients (control group). Psychological tests were carried out immediately before the withdrawal of PT and about 10 weeks later. Tests were also carried out with the control group at the same time. A significantly improved performance (using a composite score) was noted after the withdrawal of PT. The statistical evaluation of the different tests showed an significant improvement in one test of concentration and two tests of psychomotor function (tapping and pursuit rotor with the dominant hand). There was no significant change in the frequency of seizures.

Effects of the NMDA receptor antagonist memantine on the expression and development of acute opiate dependence as assessed by withdrawal-potentiated startle and hyperalgesia.

PubMed

Harris, Andrew C; Rothwell, Patrick E; Gewirtz, Jonathan C

2008-03-01

While the N-methyl-D: -aspartate (NMDA) glutamate receptor has been strongly implicated in chronic opiate dependence, relatively few studies have examined the effects of NMDA receptor antagonists on withdrawal from acute opiate exposure. The current study examined the effects of memantine, a well-tolerated NMDA receptor antagonist, on acute opiate dependence as assessed by elevations in rodent startle responding (i.e., "withdrawal-potentiated startle") and increased pain sensitivity (i.e., hyperalgesia). Administration of memantine either attenuated (5 mg/kg) or blocked (10 mg/kg) the expression of withdrawal-potentiated startle during naloxone (2.5 mg/kg)-precipitated withdrawal from a single dose of morphine sulfate (10 mg/kg). Pre-treatment with the NMDA receptor antagonist also inhibited the exacerbation of withdrawal-potentiated startle across repeated acute opiate exposures. Memantine blocked the expression of acute dependence, but was less effective in inhibiting its escalation, when hyperalgesia was used as a measure of withdrawal. These doses of memantine did not affect startle responding or nociception in otherwise drug-free animals. Data from additional control groups indicated that the effects of memantine on the expression of withdrawal were not influenced by nonspecific interactions between the NMDA antagonist and either morphine or naloxone. These findings suggest that the NMDA receptor may play a key role in the earliest stages of opiate dependence and provide further evidence that memantine may be useful for the treatment of opiate withdrawal.

Influencing the electronic interaction in diferrocenyl-1-phenyl-1H-pyrroles.

PubMed

Hildebrandt, Alexander; Lang, Heinrich

2011-11-28

Functionalised diferrocenyl-1-phenyl-1H-pyrroles were synthesised using Negishi C,C cross-coupling reactions. The influence of different substituents at the phenyl moiety on the electronic interaction was studied using electrochemistry (cyclic and square-wave voltammetry) and spectro-electrochemistry (in situ UV/Vis-NIR spectroscopy). The ferrocenyl moieties gave rise to two sequential, reversible redox processes in each of the diferrocenyl-1-phenyl-1H-pyrroles. The observed ΔE(1/2) values (ΔE(1/2) = difference between first and second oxidation) range between 420 and 480 mV. A linear relationship between the Hammett constants σ of the substituents and the separation of the redox potentials exists. The NIR measurements confirm electronic communication between the iron centers as intervalence charge transfer (IVCT) absorptions were observed in the corresponding mixed-valent monocationic species. All compounds were classified as class II systems according to Robin and Day (M. B. Robin and P. Day, Adv. Inorg. Chem., 1967, 10, 247-423). The oscillator strength of the charge transfer transition highly depends on the electron donating or electron withdrawing character of the phenyl substituents. This enables direct tuning of the intermetallic communication by simple modification of the molecule's functional group. Hence, this series of molecules may be regarded as model compounds for single molecule transistors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, A.; Tsiounis, Y.; Frankel, Y.

Recently, there has been an interest in making electronic cash protocols more practical for electronic commerce by developing e-cash which is divisible (e.g., a coin which can be spent incrementally but total purchases are limited to the monetary value of the coin). In Crypto`95, T. Okamoto presented the first practical divisible, untraceable, off-line e-cash scheme, which requires only O(log N) computations for each of the withdrawal, payment and deposit procedures, where N = (total coin value)/(smallest divisible unit). However, Okamoto`s set-up procedure is quite inefficient (on the order of 4,000 multi-exponentiations and depending on the size of the RSA modulus).more » The authors formalize the notion of range-bounded commitment, originally used in Okamoto`s account establishment protocol, and present a very efficient instantiation which allows one to construct the first truly efficient divisible e-cash system. The scheme only requires the equivalent of one (1) exponentiation for set-up, less than 2 exponentiations for withdrawal and around 20 for payment, while the size of the coin remains about 300 Bytes. Hence, the withdrawal protocol is 3 orders of magnitude faster than Okamoto`s, while the rest of the system remains equally efficient, allowing for implementation in smart-cards. Similar to Okamoto`s, the scheme is based on proofs whose cryptographic security assumptions are theoretically clarified.« less

Quantitative structure-activity relationship studies of threo-methylphenidate analogs.

PubMed

Misra, Milind; Shi, Qing; Ye, Xiaocong; Gruszecka-Kowalik, Ewa; Bu, Wei; Liu, Zhanzhu; Schweri, Margaret M; Deutsch, Howard M; Venanzi, Carol A

2010-10-15

Complementary two-dimensional (2D) and three-dimensional (3D) Quantitative Structure-Activity Relationship (QSAR) techniques were used to derive a preliminary model for the dopamine transporter (DAT) binding affinity of 80 racemic threo-methylphenidate (MP) analogs. A novel approach based on using the atom-level E-state indices of the 14 common scaffold atoms in a sphere exclusion protocol was used to identify a test set for 2D- and 3D-QSAR model validation. Comparative Molecular Field Analysis (CoMFA) contour maps based on the structure-activity data of the training set indicate that the 2' position of the phenyl ring cannot tolerate much steric bulk and that addition of electron-withdrawing groups to the 3' or 4' positions of the phenyl ring leads to improved DAT binding affinity. In particular, the optimal substituents were found to be those whose bulk is mainly in the plane of the phenyl ring. Substituents with significant bulk above or below the plane of the ring led to decreased binding affinity. Suggested alterations to be explored in the design of new compounds are the placement at the 3' and 4' position of the phenyl ring of electron-withdrawing groups that lie chiefly in the plane of the ring, for example, halogen substituents on the 3',4'-benzo analog, 79. A complementary 2D-QSAR approach-partial least squares analysis using a reduced set of Molconn-Z descriptors-supports the CoMFA structure-activity interpretation that phenyl ring substitution is a major determinant of DAT binding affinity. The potential usefulness of the CoMFA models was demonstrated by the prediction of the binding affinity of methyl 2-(naphthalen-1-yl)-2-(piperidin-2-yl)acetate, an analog not in the original data set, to be in good agreement with the experimental value. Copyright © 2010 Elsevier Ltd. All rights reserved.

Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial.

PubMed

Allsop, David J; Copeland, Jan; Lintzeris, Nicholas; Dunlop, Adrian J; Montebello, Mark; Sadler, Craig; Rivas, Gonzalo R; Holland, Rohan M; Muhleisen, Peter; Norberg, Melissa M; Booth, Jessica; McGregor, Iain S

2014-03-01

There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. To evaluate the safety and efficacy of nabiximols in treating cannabis withdrawal. A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. A 6-day regimen of nabiximols (maximum daily dose, 86.4 mg of Δ9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F8,377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between nabiximols and placebo treatment (χ21 = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of nabiximols over placebo for self-reported cannabis use (F1,48 = 0.29; P = .75), cannabis-related problems (F1,49 = 2.33; P = .14), or cannabis dependence (F1,50 < 0.01; P = .89). In a treatment-seeking cohort, nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations. anzctr.org.au Identifier: ACTRN12611000398909.

Disentangling the Roles of Approach, Activation and Valence in Instrumental and Pavlovian Responding

PubMed Central

Huys, Quentin J. M.; Cools, Roshan; Gölzer, Martin; Friedel, Eva; Heinz, Andreas; Dolan, Raymond J.; Dayan, Peter

2011-01-01

Hard-wired, Pavlovian, responses elicited by predictions of rewards and punishments exert significant benevolent and malevolent influences over instrumentally-appropriate actions. These influences come in two main groups, defined along anatomical, pharmacological, behavioural and functional lines. Investigations of the influences have so far concentrated on the groups as a whole; here we take the critical step of looking inside each group, using a detailed reinforcement learning model to distinguish effects to do with value, specific actions, and general activation or inhibition. We show a high degree of sophistication in Pavlovian influences, with appetitive Pavlovian stimuli specifically promoting approach and inhibiting withdrawal, and aversive Pavlovian stimuli promoting withdrawal and inhibiting approach. These influences account for differences in the instrumental performance of approach and withdrawal behaviours. Finally, although losses are as informative as gains, we find that subjects neglect losses in their instrumental learning. Our findings argue for a view of the Pavlovian system as a constraint or prior, facilitating learning by alleviating computational costs that come with increased flexibility. PMID:21556131

Identification of the Phenol Functionality in Deprotonated Monomeric and Dimeric Lignin Degradation Products via Tandem Mass Spectrometry Based on Ion-Molecule Reactions with Diethylmethoxyborane

NASA Astrophysics Data System (ADS)

Zhu, Hanyu; Max, Joann P.; Marcum, Christopher L.; Luo, Hao; Abu-Omar, Mahdi M.; Kenttämaa, Hilkka I.

2016-11-01

Conversion of lignin into smaller molecules provides a promising alternate and sustainable source for the valuable chemicals currently derived from crude oil. Better understanding of the chemical composition of the resulting product mixtures is essential for the optimization of such conversion processes. However, these mixtures are complex and contain isomeric molecules with a wide variety of functionalities, which makes their characterization challenging. Tandem mass spectrometry based on ion-molecule reactions has proven to be a powerful tool in functional group identification and isomer differentiation for previously unknown compounds. This study demonstrates that the identification of the phenol functionality, the most commonly observed functionality in lignin degradation products, can be achieved via ion-molecule reactions between diethylmethoxyborane (DEMB) and the deprotonated analyte in the absence of strongly electron-withdrawing substituents in the ortho- and para-positions. Either a stable DEMB adduct or an adduct that has lost a methanol molecule (DEMB adduct-MeOH) is formed for these ions. Deprotonated phenols with an adjacent phenol or hydroxymethyl functionality or a conjugated carboxylic acid functionality can be identified based on the formation of DEMB adduct-MeOH. Deprotonated compounds not containing the phenol functionality and phenols containing an electron-withdrawing ortho- or para-substituent were found to be unreactive toward diethylmethoxyborane. Hence, certain deprotonated isomeric compounds with phenol and carboxylic acid, aldehyde, carboxylic acid ester, or nitro functionalities can be differentiated via these reactions. The above mass spectrometry method was successfully coupled with high-performance liquid chromatography for the analysis of a complex biomass degradation mixture.

Molecularly Tuning the Radicaloid N-H···O═C Hydrogen Bond.

PubMed

Lu, Norman; Chung, Wei-Cheng; Ley, Rebecca M; Lin, Kwan-Yu; Francisco, Joseph S; Negishi, Ei-Ichi

2016-03-03

Substituent effects on the open shell N-H···O═C hydrogen-bond has never been reported. This study examines how 12 functional groups composed of electron donating groups (EDG), halogen atoms and electron withdrawing groups (EWG) affect the N-H···O═C hydrogen-bond properties in a six-membered cyclic model system of O═C(Y)-CH═C(X)N-H. It is found that group effects on this open shell H-bonding system are significant and have predictive trends when X = H and Y is varied. When Y is an EDG, the N-H···O═C hydrogen-bond is strengthened; and when Y is an EWG, the bond is weakened; whereas the variation in electronic properties of X group do not exhibit a significant impact upon the hydrogen bond strength. The structural impact of the stronger N-H···O═C hydrogen-bond are (1) shorter H and O distance, r(H···O) and (2) a longer N-H bond length, r(NH). The stronger N-H···O═C hydrogen-bond also acts to pull the H and O in toward one another which has an effect on the bond angles. Our findings show that there is a linear relationship between hydrogen-bond angle and N-H···O═C hydrogen-bond energy in this unusual H-bonding system. In addition, there is a linear correlation of the r(H···O) and the hydrogen bond energy. A short r(H···O) distance corresponds to a large hydrogen bond energy when Y is varied. The observed trends and findings have been validated using three different methods (UB3LYP, M06-2X, and UMP2) with two different basis sets.

Chlorophylls, ligands and assembly of light-harvesting complexes in chloroplasts

PubMed Central

Eggink, Laura L.; Chen, Min

2007-01-01

Chlorophyll (Chl) b serves an essential function in accumulation of light-harvesting complexes (LHCs) in plants. In this article, this role of Chl b is explored by considering the properties of Chls and the ligands with which they interact in the complexes. The overall properties of the Chls, not only their spectral features, are altered as consequences of chemical modifications on the periphery of the molecules. Important modifications are introduction of oxygen atoms at specific locations and reduction or desaturation of sidechains. These modifications influence formation of coordination bonds by which the central Mg atom, the Lewis acid, of Chl molecules interacts with amino acid sidechains, as the Lewis base, in proteins. Chl a is a versatile Lewis acid and interacts principally with imidazole groups but also with sidechain amides and water. The 7-formyl group on Chl b withdraws electron density toward the periphery of the molecule and consequently the positive Mg is less shielded by the molecular electron cloud than in Chl a. Chl b thus tends to form electrostatic bonds with Lewis bases with a fixed dipole, such as water and, in particular, peptide backbone carbonyl groups. The coordination bonds are enhanced by H-bonds between the protein and the 7-formyl group. These additional strong interactions with Chl b are necessary to achieve assembly of stable LHCs. PMID:17505910

Arylethynyl Substituted 9,lO-Anthraquinones: Tunable Stokes Shifts by Substitution and Solvent Polarity

NASA Technical Reports Server (NTRS)

Yang, Jinhua; Dass, Amala; Rawashdeh, Abdel-Monem M.; Sotiriou-Leventis, Chariklia; Panzner, Matthew J.; Tyson, Daniel S.; Kinder, James D.; Leventis, Nicholas

2004-01-01

2-Arylethynyl- and 2,6- and 2,7-diarylethynyl-substituted 9,lO-anthraquinones were synthesized via Sonogashira coupling reactions of 2-bromo-, 2,6-dibromo-, and 2,7-dibromo-9,10- anthraquinone with para-substituted phenylacetylenes. While the redox properties of those compounds are almost insensitive to substitution, their absorption maxima are linearly related to the Hammett constants with different slopes for electron donors and electron acceptors. ABI compounds are photoluminescent both in solution (quantum yields of emission <= 6 %), and as solids. The emission spectra have the characteristics of charge-transfer bands with large Stokes shifts (100-250 nm). The charge-transfer character of the emitting state is supported by large dipole moment differences between the ground and the excited state as concluded on the basis of molecular modeling and Lippert-Mataga correlations of the Stokes shifts with solvent polarity. Maximum Stokes shifts are attained by both electron-donating and -withdrawing groups. This is explained by a destabilization of the HOMO by electron donors and a stabilization of the LUMO by electron acceptors. X-ray crystallographic analysis of, for example, 2,7-bisphenylethynfl- 9,lO-anthraquinone reveals a monoclinic P21In space group and no indication for pi-overlap that would promote quenching, thus explaining emission from the solid state. Representative reduced forms of the title compounds were isolated as stable acetates of the corresponding dihydrs-9,10- anthraquinones. The emission of these compounds is blue-shifted relative to the parent oxidized forms and is attributed to internal transitions in the dihydro-9,lO-anthraquinone core.

Tolerance and Withdrawal From Prolonged Opioid Use in Critically Ill Children

PubMed Central

Anand, Kanwaljeet J. S.; Willson, Douglas F.; Berger, John; Harrison, Rick; Meert, Kathleen L.; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J. L.; Prodhan, Parthak; Dean, J. Michael; Nicholson, Carol

2012-01-01

OBJECTIVE After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. PATIENTS AND METHODS Relevant manuscripts published in the English language were searched in Medline by using search terms “opioid,” “opiate,” “sedation,” “analgesia,” “child,” “infant-newborn,” “tolerance,” “dependency,” “withdrawal,” “analgesic,” “receptor,” and “individual opioid drugs.” Clinical and preclinical studies were reviewed for data synthesis. RESULTS Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. CONCLUSIONS Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal. PMID:20403936

Enhancement effect on the chemiluminescence of acridinium esters under neutral conditions.

PubMed

Nakazono, Manabu; Nanbu, Shinkoh

2018-03-01

Enhancement effect on the chemiluminescence of acridinium ester derivatives under neutral conditions was investigated. Additions of phenols did not enhance the chemiluminescence intensities of acridinium ester derivatives in the presence of horseradish peroxidase and hydrogen peroxide. Additions of cetyltrimethylammonium bromide apparently enhanced the chemiluminescence intensities of phenyl 10-methyl-10λ 4 -acridine-9-carboxylate derivatives with electron-withdrawing groups at the 4-position of the phenyl group. In particular, the chemiluminescence intensity of 4-(trifluoromethyl)phenyl 10-methyl-10λ 4 -acridine-9-carboxylate trifluoromethanesulfonate salt was 5.5 times stronger in the presence of cetyltrimethylammonium bromide than in its absence at pH 7. The chemiluminescence intensity of 3,4-dicyano-phenyl 10-methyl-10λ 4 -acridine-9-carboxylate trifluoromethanesulfonate salt was 46 times stronger in the presence of cetyltrimethylammonium bromide at pH 7 than in its absence at pH 10. Copyright © 2017 John Wiley & Sons, Ltd.

Asymmetric silver-catalysed intermolecular bromotrifluoromethoxylation of alkenes with a new trifluoromethoxylation reagent

NASA Astrophysics Data System (ADS)

Guo, Shuo; Cong, Fei; Guo, Rui; Wang, Liang; Tang, Pingping

2017-06-01

Fluorinated organic compounds are becoming increasingly important in pharmaceuticals, agrochemicals and materials science. The introduction of trifluoromethoxy groups into new drugs and agrochemicals has attracted much attention due to their strongly electron-withdrawing nature and high lipophilicity. However, synthesis of trifluoromethoxylated organic molecules is difficult owing to the decomposition of trifluoromethoxide anion and β-fluoride elimination from transition-metal-trifluoromethoxide complexes, and no catalytic enantioselective trifluoromethoxylation reaction has been reported until now. Here, we present an example of an asymmetric silver-catalysed intermolecular bromotrifluoromethoxylation of alkenes with trifluoromethyl arylsulfonate (TFMS) as a new trifluoromethoxylation reagent. Compared to other trifluoromethoxylation reagents, TFMS is easily prepared and thermally stable with good reactivity. In addition, this reaction is operationally simple, scalable and proceeds under mild reaction conditions. Furthermore, broad scope and good functional group compatibility has been demonstrated by application of the method to the bromotrifluoromethoxylation of double bonds in natural products and natural product derivatives.

Design, synthesis and antimalarial evaluation of novel thiazole derivatives.

PubMed

Bueno, José María; Carda, Miguel; Crespo, Benigno; Cuñat, Ana Carmen; de Cozar, Cristina; León, María Luisa; Marco, J Alberto; Roda, Nuria; Sanz-Cervera, Juan F

2016-08-15

As part of our medicinal chemistry program's ongoing search for compounds with antimalarial activity, we prepared a series of thiazole analogs and conducted a SAR study analyzing their in vitro activities against the chloroquine-sensitive Plasmodium falciparum 3D7 strain. The results indicate that modifications of the N-aryl amide group linked to the thiazole ring are the most significant in terms of in vitro antimalarial activity, leading to compounds with high antimalarial potency and low cytotoxicity in HepG2 cell lines. Furthermore, the observed SAR implies that non-bulky, electron-withdrawing groups are preferred at ortho position on the phenyl ring, whereas small atoms such as H or F are preferred at para position. Finally, replacement of the phenyl ring by a pyridine affords a compound with similar potency, but with potentially better physicochemical properties which could constitute a new line of research for further studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased self-reported impulsivity in methamphetamine users maintaining drug abstinence.

PubMed

Jones, Hannah W; Dean, Andy C; Price, Kimberly A; London, Edythe D

2016-09-01

Impulsivity has been proposed as an important factor in the initiation and maintenance of addiction. Indirect evidence suggests that some methamphetamine users report less impulsivity when they are using methamphetamine compared to when abstaining from drug use, but this hypothesis has not been directly tested. In this study, self-reports of impulsivity were obtained from 32 methamphetamine-dependent (DSM-IV) research participants and 41 healthy control subjects, using the Barratt Impulsiveness Scale-11. The methamphetamine users were assessed during an active period of methamphetamine use, as determined through urinalysis, and again after approximately 1 week of confirmed abstinence. Control subjects likewise completed two assessments. A subset of participants also completed serial assessments of the Beck Depression Inventory (Methamphetamine Group, N = 17, Control Group, N = 38) and the Methamphetamine Withdrawal Questionnaire (Methamphetamine Group, N = 12). There was a significant interaction of group with time on impulsivity (p = 0.044), reflecting a significant increase from the first to the second assessment in the methamphetamine users (p = 0.013), but no change among healthy control subjects. In contrast, depressive and withdrawal symptoms significantly decreased between the first and second assessments in the methamphetamine users (ps ≤0.01). Change in impulsivity in methamphetamine users was not significantly correlated with change in withdrawal or depression (ps >0.05). These findings suggest that methamphetamine users report more impulsivity when abstaining from drug use, an effect that is not significantly related to methamphetamine withdrawal. Attenuation of impulsivity may reinforce continued methamphetamine use in these individuals.

[Effects of slow twisting needle insertion and tubing needle insertion at Neiguan (PC 6) on cardiovascular function: a comparative study].

PubMed

Ning, Shaoli; Zhao, Lihua; Xu, Lingjun; Huang, Yu; Pang, Yong; Huang, Dingjian

2016-01-01

To compare the effects between slow twisting needle insertion and tubing needle insertion. With cross-over design, 100 healthy young subjects (half male and half female) aged from 19 to 23 years were randomly divided into two groups by random digital table, 50 cases in each one. At the first stage, subjects in the group A were treated with slow twisting needle insertion while, subjects in,the group B were treated with tubing needle insertion. One week later, the procedure of second stage was performed alternately. The needle was inserted into Neiguan (PC 6) with two methods by one acupuncturist. The needle was retained for 5 min before removal. Five min before needle insertion as well as needle withdrawal and 30 min after needle withdrawal, ZXG-E automatic cardiovascular diagnostic apparatus was used to test cardiovascular function. At the tim of needle withdrawal, slow twisting needle insertion could improve effect work of kinetics (EWK), effective blood volume (BV) and reduce elastic expansion coefficient of blood vessel (FEK) and left ventricular spray blood impedance (VER), which was significantly different from tubing needle insertion (all P < 0.05). Thirty min after needle withdrawal, the differences of the indices of cardiovascular function between the two groups were not significant (all P > 0.05). The slow twisting needle insertion is significantly superior to tubing needle insertion on lowering vascular tension and VER, improving EWK and BV.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.N.; Xu, J.

1997-04-29

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth N.; Xu, Jide

1997-01-01

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of said chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to said 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities.

Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with Chronic Migraine: an effectiveness trial with a one-year follow-up.

PubMed

Grazzi, Licia; Sansone, Emanuela; Raggi, Alberto; D'Amico, Domenico; De Giorgio, Andrea; Leonardi, Matilde; De Torres, Laura; Salgado-García, Francisco; Andrasik, Frank

2017-12-01

Chronic Migraine (CM) is a disabling condition, worsened when associated with Medication Overuse (MO). Mindfulness is an emerging technique, effective in different pain conditions, but it has yet to be explored for CM-MO. We report the results of a study assessing a one-year course of patients' status, with the hypothesis that the effectiveness of a mindfulness-based approach would be similar to that of conventional prophylactic treatments. Patients with CM-MO (code 1.3 and 8.2 of the International Classification of Headache Disorders-3Beta) completed a withdrawal program in a day hospital setting. After withdrawal, patients were either treated with Prophylactic Medications (Med-Group), or participated in a Mindfulness-based Training (MT-Group). MT consisted of 6 weekly sessions of guided mindfulness, with patients invited to practice 7-10 min per day. Headache diaries, the headache impact test (HIT-6), the migraine disability assessment (MIDAS), state and trait anxiety (STAI Y1-Y2), and the Beck Depression Inventory (BDI) were administered before withdrawal and at each follow-up (3, 6, 12 after withdrawal) to patients from both groups. Outcome variables were analyzed in separate two-way mixed ANOVAs (Group: Mindfulness vs. Pharmacology x Time: Baseline, 3-, 6-, vs. 12-month follow-up). A total of 44 patients participated in the study, with the average age being 44.5, average headache frequency/month was 20.5, and average monthly medication intake was 18.4 pills. Data revealed a similar improvement over time in both groups for Headache Frequency (approximately 6-8 days reduction), use of Medication (approximately 7 intakes reduction), MIDAS, HIT-6 (but only for the MED-Group), and BDI; no changes on state and trait anxiety were found. Both groups revealed significant and equivalent improvement with respect to what has become a classical endpoint in this area of research, i.e. 50% or more reduction of headaches compared to baseline, and the majority of patients in each condition no longer satisfied current criteria for CM. Taken as a whole, our results suggest that the longitudinal course of patients in the MT-Group, that were not prescribed medical prophylaxis, was substantially similar to that of patients who were administered medical prophylaxis.

Efficacy of electronic cigarettes for smoking cessation.

PubMed

Orr, Katherine Kelly; Asal, Nicole J

2014-11-01

To review data demonstrating effective smoking cessation with electronic cigarettes (e-cigarettes). A literature search of MEDLINE/PubMed (1946-March 2014) was performed using the search terms e-cigarettes, electronic cigarettes, and smoking cessation. Additional references were identified from a review of literature citations. All English-language clinical studies assessing efficacy of e-cigarettes compared with baseline, placebo, or other pharmacological methods to aid in withdrawal symptoms, smoking reduction, or cessation were evaluated. A total of 6 clinical studies were included in the review. In small studies, e-cigarettes significantly decreased desire to smoke, number of cigarettes smoked per day, and exhaled carbon monoxide levels. Symptoms of nicotine withdrawal and adverse effects were variable. The most common adverse effects were nausea, headache, cough, and mouth/throat irritation. Compared with nicotine patches, e-cigarettes were associated with fewer adverse effects and higher adherence. Most studies showed a significant decrease in cigarette use acutely; however, long-term cessation was not sustained at 6 months. There is limited evidence for the effectiveness of e-cigarettes in smoking cessation; however, there may be a place in therapy to help modify smoking habits or reduce the number of cigarettes smoked. Studies available provided different administration patterns such as use while smoking, instead of smoking, or as needed. Short-term studies reviewed were small and did not necessarily evaluate cessation with a focus on parameters associated with cessation withdrawal symptoms. Though long-term safety is unknown, concerns regarding increased poisoning exposures among adults in comparison with cigarettes are alarming. © The Author(s) 2014.

48 CFR 52.214-7 - Late submissions, modifications, and withdrawals of bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... transmitted through an electronic commerce method authorized by the IFB, it was received at the initial point... Government processes resume. (e) Bids may be withdrawn by written notice received at any time before the...

Theoretical analysis of the electronic properties of the sex pheromone and its analogue derivatives in the female processionary moth Thaumetopoea pytiocampa.

PubMed

Chamorro, Ester R; Sequeira, Alfredo F; Zalazar, M Fernanda; Peruchena, Nélida M

2008-09-15

In the present work, the distribution of the electronic charge density of the natural sex pheromone, the (Z)-13-hexadecen-11-ynyl acetate, in the female processionary moth, Thaumetopoea pytiocampa, and its nine analogue derivatives was studied within the framework of the Density Functional Theory and the Atoms in Molecules (AIM) Theory at B3LYP/6-31G *//B3LYP/6-31++G * * level. Additionally, molecular electrostatic potential (MEP) maps of the previously mentioned compounds were computed and compared. Furthermore, the substitution of hydrogen atoms from the methyl group in the acetate group by electron withdrawing substituents (i.e., halogen atoms) as well as the replacement effect of hydrogen by electron donor substituents (+I effect) as methyl group, were explored. The key feature of the topological distribution of the charge density in analogue compounds, such as the variations of the topological properties encountered in the region formed by neighbouring atoms from the substitution site were presented and discussed. Using topological parameters, such as electronic charge density, Laplacian, kinetic energy density, and potential energy density evaluated at bond critical points (BCP), we provide here a detailed analysis of the nature of the chemical bonding of these molecules. In addition, the atomic properties (population, charge, energy, volume, and dipole moment) were determined on selected atoms. These properties were analyzed at the substitution site (with respect to the natural sex pheromone) and related to the biological activity and to the possible binding site with the pheromone binding protein, (PBP). Moreover, the Laplacian function of the electronic density was used to locate electrophilic regions susceptible to be attacked (by deficient electron atoms or donor hydrogen). Our results indicate that the change in the atomic properties, such as electronic population and atomic volume, are sensitive indicators of the loss of the biological activity in the analogues studied here. The crucial interaction between the acetate group of the natural sex pheromone and the PBP is most likely to be a hydrogen bonding and the substitution of hydrogen atoms by electronegative atoms in the pheromone molecule reduces the hydrogen acceptor capacity. This situation is mirrored by the diminish of the electronic population on carbon and oxygen atoms at the carbonylic group in the halo-acetate group. Additionally, the modified acetate group (with electronegative atoms) shows new charge concentration critical points or regions of concentration of charge density in which an electrophilic attack can also occur. Finally, the use of the topological analysis based in the charge density distribution and its Laplacian function, in conjunction with MEP maps provides valuable information about the steric volume and electronic requirement of the sex pheromone for binding to the PBP.

Graduation and Withdrawal from RN Programs. A Report of the Nurse Career-Pattern Study.

ERIC Educational Resources Information Center

Knopf, Lucille

Based on a larger longitudinal study, this document examines three nursing groups--those entering schools preparing registered nurses in 1962, 1965, and 1967. It describes and compares those who graduated and those who withdrew before graduation and examines the reasons why the students withdraw from both the students' and the program directors'…

Sunrayce 97 Continues Day 7 - Smith Center to St. Francis

Science.gov Websites

Angeles driver and team leader Roman Vasquez says, "We haven't had any problems. The car's been withdraw from the race yesterday due to suspension problems. The team was presented an "Inspector's . The team worked as a group in arriving at their decision to withdraw from the competition. Sunrayce 97

Is Homeopathy Effective for Hot Flashes and Other Estrogen-Withdrawal Symptoms in Breast Cancer Survivors? A Preliminary Randomized Controlled Trial

DTIC Science & Technology

2003-04-01

homeopathy may be effective in improving hot flashes and quality of life in breast cancer survivors with symptoms of estrogen withdrawal. Methods- A...scores improved significantly in both homeopathy groups compared to placebo. Results of this study suggest that a larger study should be done.

Community Resilience and the Impact of Stress: Adult Response to Israel's Withdrawal from Lebanon

ERIC Educational Resources Information Center

Kimhi, Shaul; Shamai, Michal

2004-01-01

Against the background of the Israeli withdrawal from Lebanon, we investigated the relationship between perceived community resilience and the effect of stress and life satisfaction. The research sample included 741 adults, aged 18-85. The participants were divided into four groups, three of which live close to the Israel-Lebanon border and were…

Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase inhibitors.

PubMed

Nisa, Mehr-Un; Munawar, Munawar A; Iqbal, Amber; Ahmed, Asrar; Ashraf, Muhammad; Gardener, Qurra-Tul-Ann A; Khan, Misbahul A

2017-09-29

A novel series of 5-(aroylhydrazinocarbonyl)escitalopram (58-84) have been designed, synthesized and tested for their inhibitory potential against cholinesterases. 3-Chlorobenzoyl- (71) was found to be the most potent compound of this series having IC 50 1.80 ± 0.11 μM for acetylcholinesterase (AChE) inhibition. For the butyrylcholinesterase (BChE) inhibition, 2-bromobenzoyl- (76) was the most active compound of the series with IC 50 2.11 ± 0.31 μM. Structure-activity relationship illustrated that mild electron donating groups enhanced enzyme inhibition while electron withdrawing groups reduced the inhibition except o-NO 2 . However, size and position of the substituents affected enzyme inhibitions. . In docking study of AChE, the ligands 71, 72 and 76 showed the scores of 5874, 5756 and 5666 and ACE of -64.92,-203.25 and -140.29 kcal/mol, respectively. In case of BChE, ligands 71, 76 and 81 depicted high scores 6016, 6150 and 5994 with ACE values -170.91, -256.84 and -235.97 kcal/mol, respectively. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Theoretical studies of weak interactions of formamide with methanol and its derivates

NASA Astrophysics Data System (ADS)

Zheng, Xiao-Wen; Wang, Lu; Han, Shu-Min; Cui, Xiang-Yang; Du, Chong-Yang; Liu, Tao

2015-08-01

Theoretical calculations have been performed for the complexes of formamide (FA) with methanol and its derivates (MAX, X = F, Cl, Br, NO2, H, OH, CH3, and NH2) to study their structures and properties. Substituent effects on the hydrogen bond (H-bond) strength and cooperative effect by using water and its derivatives (HOZ, Z = H, NH2, and Br) as weak interaction probe were also explored. The calculation results show that electron-donating groups strengthen the weak interaction between formamide with methanol whereas electron-withdrawing groups weaken it. The cooperativity is present for the N-HïO H-bond in MAX-FA-HOZ and the cooperative effect increases in a series HONH2, HOH, and HOBr. In addition, we investigated the interaction between FA with hypohalous acids HOY (Y = F, Cl, and Br). It was found that the weak interaction between FA and HOY became stronger with the increase of the size of halogen atom. The nature of the halogen atom has negligible impact on the strength of the H-bond in MAX-FA (X = F, Cl, and Br), whereas it has an obvious influence on the strength of the H-bond in HOY-FA (Y = F, Cl, and Br).

Effects of corticotropin-releasing factor receptor-1 antagonists on the brain stress system responses to morphine withdrawal.

PubMed

Navarro-Zaragoza, Javier; Núñez, Cristina; Laorden, M Luisa; Milanés, M Victoria

2010-05-01

The role of stress in drug addiction is well established. The negative affective states of withdrawal most probably involve recruitment of brain stress neurocircuitry [e.g., induction of hypothalamo-pituitary-adrenocortical (HPA) axis, noradrenergic activity, and corticotropin-releasing factor (CRF) activity]. The present study investigated t$he role of CRF receptor-1 subtype (CRF1R) on the response of brain stress system to morphine withdrawal. The effects of naloxone-precipitated morphine withdrawal on noradrenaline (NA) turnover in the paraventricular nucleus (PVN), HPA axis activity, signs of withdrawal, and c-Fos expression were measured in rats pretreated with vehicle, CP-154526 [N-butyl-N-ethyl-2,5-dimethyl-7-(2,4,6-trimethylphenyl)pyrrolo[3,2-e]pyrimidin-4-amine], or antalarmin (selective CRF1R antagonists). Tyrosine hydroxylase-positive neurons expressing CRF1R were seen at the level of the nucleus tractus solitarius-A(2) cell group in both control and morphine-withdrawn rats. CP-154526 and antalarmin attenuated the increases in body weight loss and irritability that were seen during naloxone-induced morphine withdrawal. Pretreatment with CRF1R antagonists resulted in no significant modification of the increased NA turnover at PVN, plasma corticosterone levels, or c-Fos expression that was seen during naloxone-induced morphine withdrawal. However, blockade of CRF1R significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropin levels. These results suggest that the CRF1R subtype may be involved in the behavioral and somatic signs and in adrenocorticotropin release (partially) during morphine withdrawal. However, CRF1R activation may not contribute to the functional interaction between NA and CRF systems in mediating morphine withdrawal-activation of brain stress neurocircuitry.

Quantifying the Clinical Significance of Cannabis Withdrawal

PubMed Central

Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

2012-01-01

Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

Dextromethorphan and Quinidine Combination for Heroin Detoxification

PubMed Central

Akerele, Evaristo; Bisaga, Adam; Sullivan, Maria A.; Garawi, Fatima; Comer, Sandra D.; Thomas, Anil A.; Nunes, Edward V.; Kleber, Herbert D.

2015-01-01

Dextromethorphan (DM) is a low-affinity, non-competitive NMDA receptor antagonist that has shown promise in pre-clinical and preliminary clinical studies for the reduction of opioid withdrawal symptoms, but when used at higher doses, it is associated with deleterious side effects attributed to its metabolite, dextrorphan. A clinical trial was therefore conducted to test the withdrawal-suppressant effect of a combination of dextromethorphan with quinidine (DM/Q). Quinidine inhibits the metabolism of dextromethorphan, reducing dextrorphan levels. Opioid-dependent patients were admitted to an inpatient unit, stabilized for three days on morphine (25 mg, sc, every six hours), and randomly assigned on day 2 to DM/Q (30 mg/30 mg, twice a day) (n = 22) or matching placebo (n = 9) prior to the discontinuation of morphine on day 4. Withdrawal symptoms, measured with the Modified Himmelsbach Opioid Withdrawal Scale (MHOWS), increased significantly on days 4 and 5 (Z = 3.70, p = .0002), and by day 6, 90% of the sample (28/31) had dropped out of the study. There were no differences between treatment groups on either outcome measure. The combination of dextromethorphan and quinidine appears ineffective as a primary treatment for opioid withdrawal. Future studies should examine dextromethorphan as an adjunct to other anti-withdrawal medications and focus more on the relationship between dextrorphan levels and withdrawal suppression. PMID:18463993

Microbial fuel cell operation using monoazo and diazo dyes as terminal electron acceptor for simultaneous decolourisation and bioelectricity generation.

PubMed

Oon, Yoong-Sin; Ong, Soon-An; Ho, Li-Ngee; Wong, Yee-Shian; Oon, Yoong-Ling; Lehl, Harvinder Kaur; Thung, Wei-Eng; Nordin, Noradiba

2017-03-05

Monoazo and diazo dyes [New coccine (NC), Acid orange 7 (AO7), Reactive red 120 (RR120) and Reactive green 19 (RG19)] were employed as electron acceptors in the abiotic cathode of microbial fuel cell. The electrons and protons generated from microbial organic oxidation at the anode which were utilized for electrochemical azo dye reduction at the cathodic chamber was successfully demonstrated. When NC was employed as the electron acceptor, the chemical oxygen demand (COD) removal and dye decolourisation efficiencies obtained at the anodic and cathodic chamber were 73±3% and 95.1±1.1%, respectively. This study demonstrated that the decolourisation rates of monoazo dyes were ∼50% higher than diazo dyes. The maximum power density in relation to NC decolourisation was 20.64mW/m 2 , corresponding to current density of 120.24mA/m 2 . The decolourisation rate and power output of different azo dyes were in the order of NC>AO7>RR120>RG19. The findings revealed that the structure of dye influenced the decolourisation and power performance of MFC. Azo dye with electron-withdrawing group at para substituent to azo bond would draw electrons from azo bond; hence the azo dye became more electrophilic and more favourable for dye reduction. Copyright © 2016 Elsevier B.V. All rights reserved.

Long-Lasting Impairment of mGluR5-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

PubMed Central

Hoffmann, Hanne Mette; Crouzin, Nadine; Moreno, Estefanía; Raivio, Noora; Fuentes, Silvia; McCormick, Peter J.; Vignes, Michel

2017-01-01

Abstract Background: Cocaine addiction continues to be a major heath concern, and despite public health intervention there is a lack of efficient pharmacological treatment options. A newly identified potential target are the group I metabotropic glutamate receptors, with allosteric modulators showing particular promise. Methods: We evaluated the capacity of group I metabotropic glutamate receptors to induce functional responses in ex vivo striatal slices from rats with (1) acute cocaine self-administration, (2) chronic cocaine self-administration, and (3) 60 days cocaine self-administration withdrawal by Western blot and extracellular recordings of synaptic transmission. Results: We found that striatal group I metabotropic glutamate receptors are the principal mediator of the mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine-induced cAMP responsive-element binding protein phosphorylation. Both acute and chronic cocaine self-administration blunted group I metabotropic glutamate receptor effects on cAMP responsive-element binding protein phosphorylation in the striatum, which correlated with the capacity to induce long-term depression, an effect that was maintained 60 days after chronic cocaine self-administration withdrawal. In the nucleus accumbens, the principal brain region mediating the rewarding effects of drugs, chronic cocaine self-administration blunted group I metabotropic glutamate receptor stimulation of extracellular signal-regulated protein kinases 1/2 and cAMP responsive-element binding protein. Interestingly, the group I metabotropic glutamate receptor antagonist/inverse-agonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride, led to a specific increase in cAMP responsive-element binding protein phosphorylation after chronic cocaine self-administration, specifically in the nucleus accumbens, but not in the striatum. Conclusions: Prolonged cocaine self-administration, through withdrawal, leads to a blunting of group I metabotropic glutamate receptor responses in the striatum. In addition, specifically in the accumbens, group I metabotropic glutamate receptor signaling to cAMP responsive-element binding protein shifts from an agonist-induced to an antagonist-induced cAMP responsive-element binding protein phosphorylation. PMID:27744406

Theoretical studies of ground and excited electronic States in a series of rhenium(i) bipyridine complexes containing diarylethynyl-based structure.

PubMed

Yang, Li; Ren, Ai-Min; Feng, Ji-Kang; Liu, Xiao-Dong; Ma, Yu-Guang; Zhang, Hong-Xing

2004-09-20

The photophysical properties, which vary as X is varied, of Re(I)-halide complexes (X2-bpy)ReICl(CO)3 (where X=ph, DAE, DNE, and DPE; ph = phenyl (1); DAE = di(amineoethynylbenzene) (2); DPE = di(phenylethynylbenzene) (3); DNE = di(nitroethynylbenzene) (4); bpy=2,2'bipyridine), are investigated using density functional theory (DFT). The electronic properties of the neutral molecules, in addition to the positive and negative ions, are studied using B3LYP functional. Excited singlet and triplet states are examined using time-dependent density functional theory (TDDFT). The low-lying excited-state geometries are optimized at the ab initio configuration interaction singlets level. As shown, the diarylethynyl-based structure is an integral component of the bpy pi-conjugated network, which results in a good planar structure. The occupied orbitals involved in the transitions have a significant mixture of metal Re and group Cl, and the lowest unoccupied orbital is a pi orbital, which extends from ligand bpy to diarylethynyl-based substituents. The luminescence for each complex originates from the lowest triplet excited states and is assigned to the mixing of MLCT and LLCT characters. Significant insights on the effects of these diarylethynyl conjugated structure and ending substituents (NH2, ph, and NO2) on absorption and emission spectra are observed by analysis of the results of the TDDFT method. The diarylethynyl-based pi-conjugated network makes both the absorption and emission spectra red-shifted compared with simple complex (bpy)ReICl(CO)3. Furthermore, an electron-releasing group (NH2) makes absorption and emission spectra blue-shift and an electron-withdrawing group (NO2) makes them red-shift. Copyright 2004 American Chemical Society

The use of O-trifluoroacetyl protection and profound influence of the nature of glycosyl acceptor in benzyl-free arabinofuranosylation.

PubMed

Abronina, Polina I; Fedina, Ksenia G; Podvalnyy, Nikita M; Zinin, Alexander I; Chizhov, Alexander O; Kondakov, Nikolay N; Torgov, Vladimir I; Kononov, Leonid O

2014-09-19

The influence of O-trifluoroacetyl (TFA) groups at different positions of thioglycoside glycosyl donors on stereoselectivity of α-arabinofuranosylation leading to corresponding disaccharides was studied. It was shown that TFA group in thioglycoside glycosyl donors, when combined with 2-O-(triisopropylsilyl) (TIPS) non-participating group, may be regarded as an electron-withdrawing protecting group that may enhance 1,2-cis-selectivity in arabinofuranosylation, the results strongly depending on the nature of glycosyl acceptor. The reactivities of the glycosyl donors were compared with those of a similar thioglycoside with O-pentafluoropropionyl groups and the known phenyl 3,5-O-(di-tert-butylsilylene)-1-thio-α-d-arabinofuranosides with 2-O-TIPS and 2-O-benzyl groups. The 'matching' in the donor-acceptor combination was found to be critical for achieving both high reactivity of glycosyl donor and β-stereoselectivity of arabinofuranosylation. The use of glycosyl donors with TFA and silyl protection may be useful in the realization of the benzyl-free approach to oligoarabinofuranosides with azido group in aglycon-convenient building blocks for the preparation of neoglycoconjugates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Modeling naturalistic craving, withdrawal, and affect during early nicotine abstinence: A pilot ecological momentary assessment study.

PubMed

Bujarski, Spencer; Roche, Daniel J O; Sheets, Erin S; Krull, Jennifer L; Guzman, Iris; Ray, Lara A

2015-04-01

Despite the critical role of withdrawal, craving, and positive affect (PA) and negative affect (NA) in smoking relapse, relatively little is known about the temporal and predictive relationship between these constructs within the first day of abstinence. This pilot study aims to characterize dynamic changes in withdrawal, craving, and affect over the course of early abstinence using ecological momentary assessment. Beginning immediately after smoking, moderate and heavy smoking participants (n = 15 per group) responded to hourly surveys assessing craving, withdrawal, NA, and PA. Univariate and multivariate multilevel random coefficient modeling was used to describe the progression of craving, withdrawal/NA, and PA and to test correlations between these constructs at the subject level over the course of early abstinence. Heavy smokers reported greater craving from 1-4 hr of abstinence and greater withdrawal/NA after 3 or more hours as compared with moderate smokers. Level of withdrawal/NA was strongly positively associated with craving, and PA was negatively correlated with craving; however, the temporal dynamics of these correlations differed substantially. The association between withdrawal/NA and craving decreased over early abstinence, whereas the reverse was observed for PA. These findings can inform experimental studies of nicotine abstinence as well as their clinical applications to smoking cessation efforts. In particular, these results help to elucidate the role of PA in nicotine abstinence by demonstrating its independent association with nicotine craving over and above withdrawal/NA. If supported by future studies, these findings can refine experimental methods and clinical approaches for smoking cessation. (c) 2015 APA, all rights reserved).

Effect on finger tremor of withdrawal of long-term treatment with propranolol or atenolol.

PubMed Central

Wharrad, H J; Birmingham, A T; Wilson, C G; Williams, E J; Roland, J M

1984-01-01

The effect of the withdrawal of long-term beta-adrenoceptor blockade on pulse rate and finger tremor was studied in 27 patients who had been treated for 2 years following an uncomplicated myocardial infarction with either atenolol, propranolol or placebo. During treatment, pulse rate was significantly lower in patients treated with propranolol or atenolol compared with placebo. Compared with the response in the placebo group the mean increase in tremor on withdrawal of propranolol was statistically significant for postural and for work tremor in both hands. A significant increase in tremor on withdrawal of atenolol occurred only in the postural position and in a narrow frequency band (left hand, 7-11 Hz; right hand, 7-9 Hz). The differences in the effect on tremor of withdrawal of treatment with propranolol or atenolol in doses which produced similar reductions in heart rate, emphasise the beta 2 classification of peripheral receptors associated with normal muscle tremor but do not exclude the involvement of beta 1-adrenoceptors. PMID:6487471

Distinct Neurochemical Adaptations Within the Nucleus Accumbens Produced by a History of Self-Administered vs Non-Contingently Administered Intravenous Methamphetamine

PubMed Central

Lominac, Kevin D; Sacramento, Arianne D; Szumlinski, Karen K; Kippin, Tod E

2012-01-01

Methamphetamine is a highly addictive psychomotor stimulant yet the neurobiological consequences of methamphetamine self-administration remain under-characterized. Thus, we employed microdialysis in rats trained to self-administer intravenous (IV) infusions of methamphetamine (METH-SA) or saline (SAL) and a group of rats receiving non-contingent IV infusions of methamphetamine (METH-NC) at 1 or 21 days withdrawal to determine the dopamine and glutamate responses in the nucleus accumbens (NAC) to a 2 mg/kg methamphetamine intraperitoneal challenge. Furthermore, basal NAC extracellular glutamate content was assessed employing no net-flux procedures in these three groups at both time points. At both 1- and 21-day withdrawal points, methamphetamine elicited a rise in extracellular dopamine in SAL animals and this effect was sensitized in METH-NC rats. However, METH-SA animals showed a much greater sensitized dopamine response to the drug challenge compared with the other groups. Additionally, acute methamphetamine decreased extracellular glutamate in both SAL and METH-NC animals at both time-points. In contrast, METH-SA rats exhibited a modest and delayed rise in glutamate at 1-day withdrawal and this rise was sensitized at 21 days withdrawal. Finally, no net-flux microdialysis revealed elevated basal glutamate and increased extraction fraction at both withdrawal time-points in METH-SA rats. Although METH-NC rats exhibited no change in the glutamate extraction fraction, they exhibited a time-dependent elevation in basal glutamate levels. These data illustrate for the first time that a history of methamphetamine self-administration produces enduring changes in NAC neurotransmission and that non-pharmacological factors have a critical role in the expression of these methamphetamine-induced neurochemical adaptations. PMID:22030712

ADHD symptoms impact smoking outcomes and withdrawal in response to Varenicline treatment for smoking cessation.

PubMed

Bidwell, L Cinnamon; Karoly, Hollis C; Hutchison, Kent E; Bryan, Angela D

2017-10-01

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with nicotine dependence and difficulty quitting smoking. Few cessation trials specifically consider the impact of ADHD on treatment outcomes, including those testing established pharmacological therapies, such as varenicline. The current study focused on the impact of pretreatment ADHD inattention (IN) and hyperactivity-impulsivity (HI) symptoms on treatment outcome in a randomized controlled trial of varenicline [N=205, average age=34.13(10.07), average baseline cigarettes per day=14.71(7.06)]. Given that varenicline's putative therapeutic mechanism is attenuation of withdrawal severity during abstinence, we also tested changes in withdrawal as a mediator of treatment effects in high and low ADHD groups. ADHD symptom severity in this sample was in the subclinical range. Cessation was associated with HI, but not IN, such that high HI individuals on varenicline reported the lowest smoking levels at the end of treatment across all groups (3.06cig/day for high HI vs 4.02cig/day for low HI). Individuals with high HI who received placebo had the highest smoking at the end of treatment (7.69cigs/day for high HI vs 5.56cig/day for low HI). Patterns continued at follow-up. Varenicline significantly reduced withdrawal for those with high HI, but not low HI. However, path models did not support an indirect effect of medication on reducing smoking via withdrawal in either group, suggesting that unmeasured variables are involved in varenicline's effect on reducing smoking. These data add to a gap in the smoking cessation literature regarding the impact of ADHD symptoms on the efficacy and mechanisms of frontline pharmacological treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re-exposure: Effects on striatal dopamine and opioid systems in C57BL/6J mice

PubMed Central

Zhang, Yong; Schlussman, Stefan D.; Rabkin, Jacqui; Butelman, Eduardo R.; Ho, Ann; Kreek, Mary Jeanne

2013-01-01

Cocaine addiction is a chronic relapsing disease with periods of chronic escalating self-exposure, separated by periods of abstinence/withdrawal of varying duration. Few studies compare such cycles in preclinical models. This study models an “addiction-like cycle” in mice to determine neurochemical/molecular alterations that underlie the chronic, relapsing nature of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14-day saline/14-day withdrawal /13-day saline + 1-day cocaine), chronic cocaine exposure (14 day cocaine) or chronic re-exposure (14-day cocaine/14-day withdrawal /14-day cocaine). Escalating-dose binge cocaine (15-30 mg/kg/injection x 3/day, i.p. at hourly intervals) or saline (14-day saline) was administered, modeling initial exposure. In “re-exposure” groups, after a 14-day injection-free period (modeling abstinence/withdrawal), mice that had received cocaine were re-injected with 14-day escalating-dose binge cocaine, whereas controls received saline. Microdialysis was conducted on the 14th day of exposure or re-exposure to determine striatal dopamine content. Messenger RNA levels of preprodynorphin (Pdyn), dopamine D1 (Drd1) and D2 (Drd2) in the caudate putamen were determined by real-time PCR. Basal striatal dopamine levels were lower in mice after 14-day escalating exposure or re-exposure than in those in the acute cocaine group and controls. Pdyn mRNA levels were higher in the cocaine groups than in controls. Long-term adaptation was observed across the stages of this addiction-like cycle, in that the effects of cocaine on dopamine levels were increased after re-exposure compared to exposure. Changes in striatal dopaminergic responses across chronic escalating cocaine exposure and re-exposure are a central feature of the neurobiology of relapsing addictive states. PMID:23164614

Clomiphene citrate before and after withdrawal bleeding for induction of ovulation in women with polycystic ovary syndrome: Randomized cross-over trial.

PubMed

Elbohoty, Ahmed E H; Amer, Mohamed; Abdelmoaz, Mohamed

2016-08-01

To compare the ovarian response to early versus late clomiphene citrate (CC) in women with polycystic ovary syndrome (PCOS). This cross-over randomized controlled clinical trial included 90 infertile amenorrheic women with PCOS. After inducing withdrawal bleeding, patients were randomly divided into two equal groups to receive ovulation induction with CC 100 mg/day for 5 days. Group I started treatment the next day after finishing medroxyprogesterone acetate course for a menstrual cycle, and after a washout period of another menstrual cycle, the treatment was shifted to start on day 2 of withdrawal bleeding. Group II received a reversed protocol: late then early treatment. Women were followed up on transvaginal ultrasonography to monitor follicular growth, endometrial thickness and evidence of ovulation. Human chorionic gonadotropin 10 000 IU was given i.m. to trigger ovulation when at least one mature follicle measured ≥18 mm at day 14. In all cases, early induction protocol resulted in significantly higher proportion of ovulating patients, thicker endometrium and higher number of follicles 14-17 mm in diameter, ≥ 18 mm in diameter and total number of follicles (P < 0.001 for all comparisons). In women with PCOS, early initiation of CC before withdrawal bleeding or during the last days of the luteal phase can achieve a better ovulatory response. © 2016 Japan Society of Obstetrics and Gynecology.

Association of testosterone and BDNF serum levels with craving during alcohol withdrawal.

PubMed

Heberlein, Annemarie; Lenz, Bernd; Opfermann, Birgitt; Gröschl, Michael; Janke, Eva; Stange, Katrin; Groh, Adrian; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas

2016-08-01

Preclinical and clinical studies show associations between testosterone and brain-derived neurotrophic growth factor (BDNF) serum levels. BDNF and testosterone have been independently reported to influence alcohol consumption. Therefore, we aimed to investigate a possible interplay of testosterone and BDNF contributing to alcohol dependence. Regarding possible interplay of testosterone and BDNF and the activity of the hypothalamic pituitary axis (HPA), we included cortisol serum levels in our research. We investigated testosterone and BDNF serum levels in a sample of 99 male alcohol-dependent patients during alcohol withdrawal (day 1, 7, and 14) and compared them to a healthy male control group (n = 17). The testosterone serum levels were significantly (p < 0.001) higher in the patients' group than in the control group and decreased significantly during alcohol withdrawal (p < 0.001). The decrease of testosterone serum levels during alcohol withdrawal (days 1-7) was significantly associated with the BDNF serum levels (day 1: p = 0.008). In a subgroup of patients showing high cortisol serum levels (putatively mirroring high HPA activity), we found a significant association of BDNF and testosterone as well as with alcohol craving measured by the Obsessive and Compulsive Drinking Scale (OCDS). Our data suggest a possible association of BDNF and testosterone serum levels, which may be relevant for the symptomatology of alcohol dependence. Further studies are needed to clarify our results. Copyright © 2016 Elsevier Inc. All rights reserved.

Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.

PubMed

Shiraki, Hiroaki; Kozar, Michael P; Melendez, Victor; Hudson, Thomas H; Ohrt, Colin; Magill, Alan J; Lin, Ai J

2011-01-13

In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivatives was prepared and assessed for antimalarial activities. The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 min, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth. The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone. Analogues with electron donating groups showed better activity than those with electron withdrawing substituents. Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC(50) data. The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests.

The synthesis and characterization of azocalix[4]arene based chemosensors and investigation of their properties

NASA Astrophysics Data System (ADS)

Elçin, Serkan; Çılgı, Gülbanu Koyundereli; Bayrakdar, Alpaslan; Deligöz, Hasalettin

2015-05-01

In the present study, azocalix[4]arenes were prepared by linking 4-methoxy, 4-methyl, 4-ethyl, 4-chloro, 4-bromo and 4-nitroaniline to calix[4]arene through a diazo-coupling reaction. A new family of azocalix[4]arene tetraester derivatives, (4a-f), have been prepared with the incorporation of ethyl ester units to azocalix[4]arene. Characterization of the synthesized azocalix[4]arenes was carried using elemental analyses, UV-vis, FT-IR and 1H NMR spectroscopic techniques. The effect of varying pH levels and solvent types on the absorption ability of azocalix[n]arenes substituted with electron-donating and electron-withdrawing groups was examined. Thermal decomposition of azocalix[4]arene derivatives (4a-f) was investigated by means of thermogravimetry (TG), differential thermogravimetry (DTG) and differential thermal analysis (DTA) analyses. In conclusion of the examination of the extraction we found a selectivity characteristic of these compounds toward Ag+, Hg+ and Hg2+ cations.

Activation of the SN2 Reaction by Adjacent π Systems: The Critical Role of Electrostatic Interactions and of Dissociative Character.

PubMed

Robiette, Raphaël; Trieu-Van, Tran; Aggarwal, Varinder K; Harvey, Jeremy N

2016-01-27

The activation of the SN2 reaction by π systems is well documented in textbooks. It has been shown previously that this is not primarily due to classical (hyper)conjugative effects. Instead, π-conjugated substituents enhance favorable substrate-nucleophile electrostatic interactions, with electron-withdrawing groups (EWG) on the sp(2) system leading to even stronger activation. Herein we report computational and experimental results which show that this activation by sp(2) EWG-substitution only occurs in a fairly limited number of cases, when the nucleophile involves strong electrostatic interactions (usually strongly basic negatively charged nucleophiles). In other cases, where bond breaking is more advanced than bond making at the transition state, electrophile-nucleophile electrostatic interactions are less important. In such cases, (hyper)conjugative electronic effects determine the reactivity, and EWG-substitution leads to decreased reactivity. The basicity of the nucleophile as well as solvent effects can help to determine which of these two regimes occurs for a given electrophile.

Mesomeric Effects of Graphene Modified with Diazonium Salts: Substituent Type and Position Influence its Properties.

PubMed

Bouša, Daniel; Jankovský, Ondřej; Sedmidubský, David; Luxa, Jan; Šturala, Jiří; Pumera, Martin; Sofer, Zdeněk

2015-12-01

In the last decade, graphene and graphene derivatives have become some of the most intensively studied materials. Tuning of the electronic and electrochemical properties of graphene is of paramount importance. In this study, six diazonium-modified graphenes containing different functional groups according to the diazonium salt precursor were investigated. These diazonium moieties have a strong mesomeric (resonance) effect and act as either electron-donating or -withdrawing species. Different graphene precursors, such as thermally and chemically reduced graphenes were studied. All the products were characterized in detail by elemental combustion analysis, FTIR spectroscopy, Raman spectroscopy, high-resolution X-ray photoelectron spectroscopy (XPS), and cyclic voltammetry. Resistivity and zeta potential measurements were consistent with theoretical (DFT) calculations. The results show that chemical modification of graphene by diazotation strongly influences its properties, creating a huge application potential in microelectronics, energy storage and conversion devices, and electrocatalysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative evaluation of therapy with L-thyroxine versus no treatment in children with idiopathic and mild subclinical hypothyroidism.

PubMed

Wasniewska, Malgorzata; Corrias, Andrea; Aversa, Tommaso; Valenzise, Mariella; Mussa, Alessandro; De Martino, Lucia; Lombardo, Fortunato; De Luca, Filippo; Salerno, Mariacarolina

2012-01-01

The question of whether children with subclinical hypothyroidism (SH) should be treated or not is controversial due to the lack of studies on outcomes of SH children treated with L-thyroxine (L-T(4)) versus those receiving no therapy. (a) To evaluate thyroid tests under L-T(4) and after therapy withdrawal in 69 SH children (group A) and (b) to compare our results with those recorded in 92 untreated children (group B). Group A children were treated for 24 months and TSH and FT(4) levels 3 months after therapy withdrawal were compared with those measured in group B at the end of follow-up in order to investigate treatment effects. The prevalence of children who had normalized TSH at the end of follow-up was higher in group A, but the prevalence of those who had normalized or maintained unchanged TSH was similar in the two groups, as was the prevalence of children who exhibited a TSH increase >10 mU/l. In group A, TSH values at 27 months were associated with baseline values. (a) Two-year treatment in SH children is unable to modify posttherapy outcome of hyperthyrotropinemia; (b) therapy is unable to prevent the risk of further TSH increase after treatment withdrawal, and (c) posttherapy TSH outcome is conditioned by baseline TSH. Copyright © 2012 S. Karger AG, Basel.

The effect of renin-angiotensin system blockade on renal protection in chronic kidney disease patients with hyperkalemia.

PubMed

Lee, Ju-Hyun; Kwon, Young Eun; Park, Jung Tak; Lee, Mi Jung; Oh, Hyung Jung; Han, Seung Hyeok; Kang, Shin-Wook; Choi, Kyu Hun; Yoo, Tae-Hyun

2014-12-01

The aim of this study was to determine the effects of renin-angiotensin system (RAS) blockade maintenance on renal protection in chronic kidney disease (CKD) patients with hyperkalemia occurring during treatment with RAS blockade. CKD III or IV patients, who were prescribed with RAS blockers and also had hyperkalemia, were included. The study population was divided into two groups based on maintenance or withdrawal of RAS blocker. Renal outcomes (doubling of creatinine or end-stage renal disease) and incidence of hyperkalemia were compared between the two groups. Out of 258 subjects who developed hyperkalemia during treatment with RAS blockers, 150 (58.1%) patients continued on RAS blockades, while RAS blockades were discontinued for more than 3 months in the remaining 108 patients. Renal event-free survival was significantly higher in the maintenance group compared with the withdrawal group. Cox proportional hazard ratio for renal outcomes was 1.35 (95% CI: 1.08-1.92, p=0.04) in the withdrawal group compared with the maintenance group. However, the incidence of hyperkalemia and hyperkalemia-related hospitalization or mortality did not differ between the two groups. This study demonstrated that the maintenance of RAS blockade is beneficial for the preservation of renal function and relatively tolerable in patients with CKD and hyperkalemia occurring during treatment with RAS blockade. © The Author(s) 2014.

Effects of caffeine and caffeine withdrawal on mood and cognitive performance degraded by sleep restriction.

PubMed

Rogers, Peter J; Heatherley, Susan V; Hayward, Robert C; Seers, Helen E; Hill, Joanne; Kane, Marian

2005-06-01

It has been suggested that caffeine is most likely to benefit mood and performance when alertness is low. To measure the effects of caffeine on psychomotor and cognitive performance, mood, blood pressure and heart rate in sleep-restricted participants. To do this in a group of participants who had also been previously deprived of caffeine for 3 weeks, thereby potentially removing the confounding effects of acute caffeine withdrawal. Participants were moderate to moderate-high caffeine consumers who were provided with either decaffeinated tea and/or coffee for 3 weeks (LTW) or regular tea and/or coffee for 3 weeks (overnight caffeine-withdrawn participants, ONW). Then, following overnight caffeine abstinence, they were tested on a battery of tasks assessing mood, cognitive performance, etc. before and after receiving caffeine (1.2 mg/kg) or on another day after receiving placebo. Final analyses were based on 17 long-term caffeine-withdrawn participants (LTW) and 17 ONW participants whose salivary caffeine levels on each test day confirmed probable compliance with the instructions concerning restrictions on consumption of caffeine-containing drinks. Acute caffeine withdrawal (ONW) had a number of negative effects, including impairment of cognitive performance, increased headache, and reduced alertness and clear-headedness. Caffeine (versus placebo) did not significantly improve cognitive performance in LTW participants, although it prevented further deterioration of performance in ONW participants. Caffeine increased tapping speed (but tended to impair hand steadiness), increased blood pressure, and had some effects on mood in both groups. The findings provide strong support for the withdrawal reversal hypothesis. In particular, cognitive performance was found to be affected adversely by acute caffeine withdrawal and, even in the context of alertness lowered by sleep restriction, cognitive performance was not improved by caffeine in the absence of these withdrawal effects. Different patterns of effects (or lack of effects) of caffeine and caffeine withdrawal were found for other variables, but overall these results also suggest that there is little benefit to be gained from caffeine consumption.

Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat.

PubMed

Economidou, Daina; Cippitelli, Andrea; Stopponi, Serena; Braconi, Simone; Clementi, Stefano; Ubaldi, Massimo; Martin-Fardon, Rèmi; Weiss, Friedbert; Massi, Maurizio; Ciccocioppo, Roberto

2011-04-01

Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol-seeking behavior induced by environmental conditioning factors or by stress in rats. In this study, we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. For this purpose, animals were subjected to a 6-day chronic alcohol intoxication (by intragastric administration), and at 8, 10, and 12 hours following cessation of alcohol exposure, they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0, and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment, an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12 hour later were tested in the EPM following ICV N/OFQ (0.0, 1.0, and 2.0 μg/rat). Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. These findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. Copyright © 2011 by the Research Society on Alcoholism.

[Changes of telemetry electrical activity in the infralimbic cortex of morphine-dependent rats with extinguished drug-seeking behavior].

PubMed

Li, Jing; Pan, Qunwan; Zhu, Zaiman; Li, Min; Bai, Yu; Yu, Ran

2015-05-01

To investigate the changes of telemetry electrical activity in the infralimbic cortex (IL) of morphine-dependent rats with extinguished drug-seeking behavior. SD rats were randomly divided into model group and control group and received operations of brain stereotaxic electrode embedding in the IL. The rats in the model group were induced to acquire morphine dependence and then received subsequent extinction training, and the changes of electrical activity in the IL were recorded with a physical wireless telemetry system. In rats with morphine dependence, the time staying in the white box was significantly longer on days 1 and 2 after withdrawal than that before morphine injection and that of the control rats, but was obviously reduced on days 1 and 2 after extinction training to the control level. Compared with the control group, the morphine-dependent rats on day 2 following withdrawal showed significantly increased β wave and decreased δ wave when they stayed in the white box but significantly increased δ wave and decreased α wave and β wave when they shuttled from the black to the white box. On day 2 of extinction, the model rats, when staying in the white box, showed significantly decreased θ wave compared with that of the control rats group but decreased β wave and θ wave and increased δ wave compared with those in the withdrawal period. When they shuttled from black to white box, the model rats showed decreased δ wave and increased α wave and β wave compared with those in the withdrawal period. Morphine-dependent rats have abnormal changes of electrical activity in the IL in drug-seeking extinction to affect their drug-seeking motive and inhibit the expression and maintenance of drug-seeking behaviors.

Retirada do leito após a descontinuação da ventilação mecânica: há repercussão na mortalidade e no tempo de permanência na unidade de terapia intensiva?

PubMed

Soares, Thiago Rios; Avena, Kátia de Miranda; Olivieri, Flávia Milholo; Feijó, Luciana Ferreira; Mendes, Kristine Menezes Barberino; Souza Filho, Sydney Agareno de; Gomes, André Mansur de Carvalho Guanaes

2010-03-01

To describe the withdrawal of the bed frequency in mechanic ventilation patients and its impact on mortality and length of stay in the intensive care unit. This was a retrospective cohort study in mechanical ventilation patients. Clinical and epidemiological variables, withdrawal of bed related motor therapy, intensive care unit length of stay and mortality were evaluated. We studied 91 patients, mean age of 62.5± 18.8 years, predominantly female (52%) and mean intensive care unit length of stay of 07 days (95% CI, 8-13 days). Considering the withdrawal of the bed or not, no difference was observed between groups regarding length of stay in intensive care unit. Patients who were withdrawn of bed had a lower clinical severity. Their mortality rate was 29.7%. The not withdrawn of bed group had higher both actual and expected mortality. Patients withdrawn of bed following mechanical ventilation discontinuation showed lower mortality. It is suggested that early intensive care unit mobilization and withdrawal of bed should be stimulated.

Differences in social support of caregivers living with partners suffering from COPD or dementia.

PubMed

Nordtug, Bente; Krokstad, Steinar; Sletvold, Olav; Holen, Are

2013-05-01

Future patients with chronic diseases will probably remain longer in their homes. To enable family caregivers to meet these challenges, public services and informal support are essential. This study compared social support between home-dwelling caregivers of partners with chronic obstructive pulmonary disease or dementia. A cross-sectional study of 206 caregivers. Professional aid was quantified by the services utilised. Informal support from family and friends was rated by the number of helping persons and the degree of social withdrawal. The Medical Outcomes Study Social Support Survey Form captured perceived social support. For both diseases, increased severity correlated with more utilisation of professional aid. The chronic obstructive pulmonary disease group perceived more social support, reported less social withdrawal and higher numbers of helping persons. Ill partners' aggressive behaviour reduced perceived support. The use of professional aid was negatively associated with the ill partner's level of self-care, and positively correlated with social withdrawal. Professional aid was more utilised by the dementia group and by men. Differences in caregivers' needs for social support were related to their partner's disease. Counteracting social withdrawal, considering type of illness and gender differences may increase the quality of informal care. © 2011 Blackwell Publishing Ltd.

Methods to evaluate functional nerve recovery in adult rats: walking track analysis, video analysis and the withdrawal reflex.

PubMed

Dijkstra, J R; Meek, M F; Robinson, P H; Gramsbergen, A

2000-03-15

The aim of this study was to compare different methods for the evaluation of functional nerve recovery. Three groups of adult male Wistar rats were studied. In group A, a 12-mm gap between nerve ends was bridged by an autologous nerve graft; in rats of group B we performed a crush lesion of the sciatic nerve and group C consisted of non-operated control rats. The withdrawal reflex, elicited by an electric stimulus, was used to evaluate the recovery of sensory nerve function. To investigate motor nerve recovery we analyzed the walking pattern. Three different methods were used to obtain data for footprint analysis: photographic paper with thickened film developer on the paws, normal white paper with finger paint, and video recordings. The footprints were used to calculate the sciatic function index (SFI). From the video recordings, we also analyzed stepcycles. The withdrawal reflex is a convenient and reproducible test for the evaluation of global sensory nerve recovery. Recording walking movements on video and the analysis of footplacing is a perfect although time-consuming method for the evaluation of functional aspects of motor nerve recovery.

Effect of CPAP Withdrawal on BP in OSA: Data from Three Randomized Controlled Trials.

PubMed

Schwarz, Esther I; Schlatzer, Christian; Rossi, Valentina A; Stradling, John R; Kohler, Malcolm

2016-12-01

Based on meta-analyses, the BP-lowering effect of CPAP therapy in patients with OSA is reported to be approximately 2 to 3 mm Hg. This figure is derived from heterogeneous trials, which are often limited by poor CPAP adherence, and thus the treatment effect may possibly be underestimated. We analyzed morning BP data from three randomized controlled CPAP withdrawal trials, which included only patients with optimal CPAP compliance. Within the three trials, 149 patients with OSA who were receiving CPAP were randomized to continue therapeutic CPAP (n = 65) or to withdraw CPAP (n = 84) for 2 weeks. Morning BP was measured at home before and after sleep studies in the hospital. CPAP withdrawal was associated with a return of OSA (apnea-hypopnea index [AHI] at a baseline of 2.8/h and at follow-up of 33.2/h). Office systolic BP (SBP) increased in the CPAP withdrawal group compared with the CPAP continuation group by +5.4 mm Hg (95% CI, 1.8-8.9 mm Hg; P = .003) and in the home SBP group by +9.0 mm Hg (95% CI, 5.7-12.3 mm Hg; P < .001). Office diastolic BP (DBP) increased by +5.0 mm Hg (95% CI, 2.7-7.3 mm Hg; P < .001), and home DBP increased by +7.8 mm Hg (95% CI, 5.6-10.4 mm Hg; P < .001). AHI, baseline home SBP, use of statin drugs, sex, and the number of antihypertensive drugs prescribed were all independently associated with SBP change in multivariate analysis, controlling for age, BMI, smoking status, diabetes, and sleepiness. CPAP withdrawal results in a clinically relevant increase in BP, which is considerably higher than in conventional CPAP trials; it is also underestimated when office BP is used. Greater OSA severity is associated with a higher BP rise in response to CPAP withdrawal. ClinicalTrials.gov; No.: NCT01332175 and NCT01797653) URL: www.clinicaltrials.gov and ISRCTN registry (ISRCTN 93153804) URL: http://www.isrctn.com/. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

[Evaluation of selected socioeconomic factors in patients with acute ethanol intoxication and alcohol withdrawal syndrome].

PubMed

Lukasik-Głębocka, Magdalena; Sommerfeld, Karina

2014-01-01

Ethanol is commonly overused psychoactive substance in Poland and all around the world. It causes addiction, which occurs as a result of its chronic administration. One of the main symptoms of addiction is hunger due to psychoactive substance that prevents interruption of its adoption and contributes to relapse drinking. Acute poisoning with ethyl alcohol and alcohol withdrawal syndrome are diseases causing a potential danger to life. The prevalence of use and abuse of alcoholic beverages is a potential risk, causing health problems, including permanent damage of the central and peripheral nervous system and socio-economic problems. The aim of this study is to analyze certain aspects of the socio-economic situation of the patients hospitalized in the Department of Toxicology in Raszeja City Hospital in Poznan due to acute ethanol intoxication or alcohol withdrawal syndrome in 2010. 299 patients history was evaluated, among which 161 were treated for acute intoxication with ethanol and 138 due to alcohol withdrawal syndrome. Objects of interest were elements of subjective tests including: marital status of patients, their education and professional activity and the problem of homelessness. The study group consisted of 299 patients in age from 16 to 77 years, hospitalized in the Department of Toxicology in Raszeja City Hospital in Poznan due to acute ethanol intoxication or alcohol withdrawal syndrome. It was found that the largest group consisted of patients remaining married (42.81%) and unmarried (30.43%). Alcohol abuse affects people of all levels of education. In the present study, most patients had a vocational education (37.79%) and medium (23.08%). Patients were analyzed in terms of economic activity, among which about 40% were unemployed. In the whole group more than 10% of those were homeless. Ethyl alcohol intoxication and alcohol withdrawal represents a significant hazard. As a result of reliance, patients lose control of alcohol consumption and they cannot reduce the amount and the time of its adoption. Reducing the dose of alcohol can lead to unpleasant withdrawal symptoms that the patient eliminate by adopting another dose. Typical is to continue the alcohol consumption despite knowledge of its harmful health and difficulties such as professional (problems at work or loss), financial (lack of livelihood, poverty) and interpersonal (loss of friends, marriage breakdown, loss of relationships with relatives).

Recurrence of IgA nephropathy after kidney transplantation in steroid continuation versus early steroid-withdrawal regimens: a retrospective analysis of the UNOS/OPTN database.

PubMed

Leeaphorn, Napat; Garg, Neetika; Khankin, Eliyahu V; Cardarelli, Francesca; Pavlakis, Martha

2018-02-01

In the past 20 years, there has been an increase in use of steroid-withdrawal regimens in kidney transplantation. However, steroid withdrawal may be associated with an increased risk of recurrent IgA nephropathy (IgAN). Using United Network of (Organ Sharing/Organ Procurement and Transplantation Network) UNOS/OPTN data, we analyzed adult patients with end-stage renal disease (ESRD) due to IgAN who received their first kidney transplant between 2000 and 2014. For the primary outcome, we used a competing risk analysis to compare the cumulative incidence of graft loss due to IgAN recurrence between early steroid-withdrawal (ESW) and steroid continuation groups. The secondary outcomes were patient survival and death-censored graft survival (DCGS). A total of 9690 recipients were included (2831 in ESW group and 6859 in steroid continuation group). In total, 1238 recipients experienced graft loss, of which 191 (15.43%) were due to IgAN recurrence. In multivariable analysis, steroid use was associated with a decreased risk of recurrence (subdistribution hazard ratio 0.666, 95% CI 0.482-0.921; P = 0.014). Patient survival and DCGS were not different between the two groups. In the USA, ESW in transplant for ESRD due to IgAN is associated with a higher risk of graft loss due to disease recurrence. Future prospective studies are warranted to further address which patients with IgAN would benefit from steroid continuation. © 2017 Steunstichting ESOT.

Hypnotics. Options to help your patients stop.

PubMed

Woodward, M

2000-10-01

There are a wide range of reasons why hypnotic agents may be started, but there is substantive evidence that they are often overused or misused. To review the reasons for stopping hypnotic agents, how to detect their use, how to facilitate the decision to withdraw and how to most effectively achieve withdrawal. In this article, the target group is using but not intentionally abusing hypnotic agents. In many cases it is possible for patients to permanently stop using hypnotic drugs. Withdrawal can generally be achieved in the community, using a gradual taper regimen, although it is often a difficult process and is more effective when the patient is aware of the health benefits to be gained from withdrawal. Once withdrawn, other approaches to maintain sleep need to be reinforced to reduce the risk of recommencing hypnotic therapy.

[Effect of rocuronium administration rate and remifentanil on prevention of rocuronium injection pain in pediatric cases].

PubMed

Şimşek Ülkü, Hatice; Güneş, Yasemin; Ilgınel, Murat; Biricik, Ebru; Karacaer, Feride

2017-10-01

In this study, we aimed to determine the effect of remifentanil administration prior to slow and fast rocuronium infusion on hemodynamic changes and rocuronium injection pain in pediatric patients. In total, 120 5-15-year-old ASA score I/II pediatric patients were included in the study. Group A: slow rocuronium injection-saline; group B: slow rocuronium injection (0.6 mg/kg IV)-remifentanyl; group C: fast rocuronium injection-saline; and group D: fast rocuronium injection-remifentanyl. Withdrawal movement after rocuronium injection was recorded based on a 3-point response to withdrawal score. Hemodynamic parameters were recorded. One minute after rocuronium injection, HR values were found to be lower in remifentanil groups (p: 0.0001; 101.4±22.1, p: 0.003; 99.8±18.3 in group B and D, respectively) compared with those in placebo groups (p: 0.025; 107.4±21.7, p: 0.012; 114.0±16.4 in group A and C, respectively). With respect to the response to withdrawal scores, unresponsiveness rates were the highest in group B (66.7%) and group D (70%). The number of non-responder patients was 9 in saline-administered groups (group A and C), whereas it was 20 and 21 in remifentanil-administered groups (group B and D, respectively). Generalized responses were observed predominantly in groups A (20%) and C (20%). Generalized responses were highest in groups A (20%, n=6) and C (20%, n=6). There was no impact of infusion speed on rocuronium injection pain in pediatric cases, whereas it is concluded that remifentanil administration prior to rocuronium injection considerably reduced rocuronium injection pain regardless of injection speed and without serious hemodynamic changes.

Relative efficacy and tolerability of etoricoxib, celecoxib, and naproxen in the treatment of osteoarthritis : A Bayesian network meta-analysis of randomized controlled trials based on patient withdrawal.

PubMed

Song, Gwan Gyu; Seo, Young Ho; Kim, Jae-Hoon; Choi, Sung Jae; Ji, Jong Dae; Lee, Young Ho

2016-06-01

This study aimed to assess the relative efficacy and tolerability of etoricoxib, celecoxib, and naproxen at recommended dosages in patients with osteoarthritis (OA). Randomized controlled trials (RCTs) examining the efficacy and tolerability of etoricoxib 30-60 mg, celecoxib 200-400 mg, and naproxen 1000 mg, based on the number of patient withdrawals among those with OA, were included in this network meta-analysis. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs. Eight RCTs, including 5,942 patients, met the inclusion criteria. The proportion of patient withdrawals due to lack of efficacy was significantly lower in the etoricoxib 30-60 mg (OR 0.21, 95 % CrI 0.12-0.38), celecoxib 200-400 mg (OR 0.29, 95 % CrI 0.18-0.47), and naproxen 1000 mg (OR 0.31, 95 % CrI 0.18-0.51) groups than in the placebo group. The number of patient withdrawals due to lack of efficacy tended to be lower in the etoricoxib 30-60 mg group than in the naproxen 1000 mg and celecoxib 200-400 mg groups, although they did not reach statistical significance (OR 0.68, 95 % CrI 0.36-1.33 and OR 0.70, 95 % CrI 0.38-1.37, respectively). Ranking probabilities based on the surface under the cumulative ranking curve (SUCRA) indicated that etoricoxib 30-60 mg had the highest probability of being the best treatment based on the number of withdrawals due to lack of efficacy (SUCRA = 0.9168) followed by celecoxib 200-400 mg (SUCRA = 0.5659), naproxen 1000 mg (SUCRA = 0.5171), and placebo (SUCRA = 0.000189). With respect to tolerability, the number of withdrawals due to adverse events was not significantly different among etoricoxib, celecoxib, naproxen, and placebo, although it tended to be lower with etoricoxib and placebo. Etoricoxib 30-60 mg, celecoxib 200-400 mg, and naproxen 1000 mg were more efficacious than placebo. However, there was no significant difference in efficacy and tolerability between the medications.

Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant and Non-Pregnant Smokers.

PubMed

Berlin, Ivan; Singleton, Edward G; Heishman, Stephen J

2016-04-01

Although pregnant smokers are aware of the negative peri- and postnatal health consequences of smoking, the cessation rate in pregnancy is low, raising the question of why pregnant smokers have difficulty quitting. Reasons might be that pregnant smokers experience more intense craving and withdrawal symptoms than non-pregnant smokers. We compared craving and withdrawal in 306 pregnant smokers versus 93 non-pregnant women using data from two smoking cessation trials. Complete data were analyzed using pre-quit and post-quit (2 weeks after quit date) craving and withdrawal measured by the 12-item French Tobacco Craving Questionnaire (FTCQ-12) and French Minnesota Nicotine Withdrawal Scale (FMNWS). Pregnant smokers started smoking and smoked regularly earlier and succeeded far less at quitting smoking by week 2 than the general population of smokers (11% versus 43%). Post-quit date FTCQ-12 general score was higher in pregnant smokers compared to comparison groups, and was driven by elevated emotionality and expectancy. FMNWS decreased significantly less among pregnant smokers than among non-pregnant smokers. Insufficient reduction of craving and withdrawal symptoms in response to a quit attempt may partially explain why pregnant smokers may have more difficulty quitting than non-pregnant smokers. Because this was a historical comparison, findings are preliminary; however, they might foster further investigation of differences in craving and withdrawal symptoms in pregnant versus non-pregnant smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

Infants' social withdrawal symptoms assessed with a direct infant observation method in primary health care.

PubMed

Puura, Kaija; Mäntymaa, Mirjami; Luoma, Ilona; Kaukonen, Pälvi; Guedeney, Antoine; Salmelin, Raili; Tamminen, Tuula

2010-12-01

Distressed infants may withdraw from social interaction, but recognising infants' social withdrawal is difficult. The aims of the study were to see whether an infant observation method can be reliably used by front line workers, and to examine the prevalence of infants' social withdrawal symptoms. A random sample of 363 families with four, eight or 18-month-old infants participated in the study. The infants were examined by general practitioners (GPs) in well-baby clinics with the Alarm Distress BaBy Scale (ADBB), an observation method developed for clinical settings. A score of five or more on the ADBB Scale in two subsequent assessments at a two-week interval was regarded as a sign of clinically significant infant social withdrawal. Kappas were calculated for the GPs' correct rating of withdrawn/not withdrawn against a set of videotapes rated by developer of the method, Professor Guedeney and his research group. The kappas for their ratings ranged from 0.5 to 1. The frequency of infants scoring above the cut off in two subsequent assessments was 3%. The ADBB Scale is a promising method for detecting infant social withdrawal in front line services. Three percents of infants were showing sustained social withdrawal as a sign of distress in this normal population sample. Copyright © 2010 Elsevier Inc. All rights reserved.

[Contraception with levonorgestrel (Norplant) subcutaneous implants. African experience in Burkina Faso].

PubMed

Koné, B; Lankoandé, J; Ouédraogo, C M; Ouédraogo, A; Bonané, B; Dao, B; Sanou, J

1999-02-01

The subcutaneous implants from the levonorgestrel (Norplant) has been introduced in Burkina Faso in September 1992 within the context of a project assisted by a non-governmental organization (the Population Council). The aim was to reinforce the family planning programme in Burkina Faso by increasing the number of family planning methods available for the clients. 4 years after its introduction, we propose to make a report of our experience in terms of the contraception through subcutaneous implants in order to better set up an IEC campaign on this method. Within 4 years, 1,660 users benefitted from that contraceptive method. They were housewives in 65% of the cases. The age-group of 30-34 years old most used this method with 28.6%. Multipares most benefitted from this method with 64.3%. In 72% of the cases, the insertion was made during the premenstrual period. On the whole, 247 withdrawals have been made before the fourth years for various reasons. Among those reasons are cycle disorders (60 withdrawals), medical reasons (53 withdrawals), personal conveniences (47 withdrawals), weight gaining (14 withdrawals), failures (2 withdrawals). Regarding the side effects, they were mainly represented by the menstrual cycle disorders such as amenorrhoea, spotting, hypermenorrhoea in 51% of the cases. A good information and sensitization campaign should reduce the number of implants withdrawals before the fourth year of use. Moreover, a perfect knowledge of contraindications is indispensable before any prescription.

Amphetamine withdrawal differentially affects hippocampal and peripheral corticosterone levels in response to stress.

PubMed

Bray, Brenna; Scholl, Jamie L; Tu, Wenyu; Watt, Michael J; Renner, Kenneth J; Forster, Gina L

2016-08-01

Amphetamine withdrawal is associated with heightened anxiety-like behavior, which is directly driven by blunted stress-induced glucocorticoid receptor-dependent serotonin release in the ventral hippocampus. This suggests that glucocorticoid availability in the ventral hippocampus during stress may be reduced during amphetamine withdrawal. Therefore, we tested whether amphetamine withdrawal alters either peripheral or hippocampal corticosterone stress responses. Adult male rats received amphetamine (2.5mg/kg, ip) or saline for 14 days followed by 2 weeks of withdrawal. Contrary to our prediction, microdialysis samples from freely-moving rats revealed that restraint stress-induced corticosterone levels in the ventral hippocampus are enhanced by amphetamine withdrawal relative to controls. In separate groups of rats, plasma corticosterone levels increased immediately after 20min of restraint and decreased to below stress-naïve levels after 1h, indicating negative feedback regulation of corticosterone following stress. However, plasma corticosterone responses were similar in amphetamine-withdrawn and control rats. Neither amphetamine nor stress exposure significantly altered protein expression or enzyme activity of the steroidogenic enzymes 11β-hydroxysteroid dehydrogenase (11β-HSD1) or hexose-6-phosphate dehydrogenase (H6PD) in the ventral hippocampus. Our findings demonstrate for the first time that amphetamine withdrawal potentiates stress-induced corticosterone in the ventral hippocampus, which may contribute to increased behavioral stress sensitivity previously observed during amphetamine withdrawal. However, this is not mediated by either changes in plasma corticosterone or hippocampal steroidogenic enzymes. Establishing enhanced ventral hippocampal corticosterone as a direct cause of greater stress sensitivity may identify the glucocorticoid system as a novel target for treating behavioral symptoms of amphetamine withdrawal. Copyright © 2016 Elsevier B.V. All rights reserved.

Nicotine Levels, Withdrawal Symptoms, and Smoking Reduction Success in Real World Use: A Comparison of Cigarette Smokers and Dual Users of Both Cigarettes and E-Cigarettes

PubMed Central

Jorenby, Douglas E.; Smith, Stevens S.; Fiore, Michael C.; Baker, Timothy B.

2016-01-01

Introduction To evaluate how experienced dual users used cigarettes and e-cigarettes in real-world use and under different levels of cigarette availability. Methods Dual users (cigarettes + e-cigarettes; n=74) and a smoke-only group (just cigarettes; n=74) engaged in a 26-day study with two ad lib use intervals, a week of 75% cigarette reduction and three days of 100% cigarette reduction. After a week of ad lib use of products, all participants were asked to reduce smoking by 75% (dual users were free to use their e-cigarettes as they wished), followed by another week of ad lib use. All participants were then asked to reduce smoking by 100% (cessation) for three days. Primary outcomes were biological samples (carbon monoxide, urinary nicotine and cotinine). Participants also provided real-time reports of product use, craving, and withdrawal symptoms using a smartphone app. Results Dual users did not smoke fewer cigarettes than smoke-only participants during ad lib periods, but quadrupled their use of e-cigarettes during smoking reduction periods. Dual users were significantly more likely to maintain 100% reduction (97.1% vs. 81.2%). Amongst women, dual use was associated with higher nicotine levels and withdrawal suppression. Discussion Among a group of experienced dual users, e-cigarettes helped maintain smoking reduction and reduced some withdrawal symptoms, although both withdrawal symptoms and nicotine levels varied as a function of gender. PMID:27883949

Nicotine levels, withdrawal symptoms, and smoking reduction success in real world use: A comparison of cigarette smokers and dual users of both cigarettes and E-cigarettes.

PubMed

Jorenby, Douglas E; Smith, Stevens S; Fiore, Michael C; Baker, Timothy B

2017-01-01

To evaluate how experienced dual users used cigarettes and e-cigarettes in real-world use and under different levels of cigarette availability. Dual users (cigarettes+e-cigarettes; n=74) and a smoke-only group (just cigarettes; n=74) engaged in a 26-day study with two ad lib use intervals, a week of 75% cigarette reduction and three days of 100% cigarette reduction. After a week of ad lib use of products, all participants were asked to reduce smoking by 75% (dual users were free to use their e-cigarettes as they wished), followed by another week of ad lib use. All participants were then asked to reduce smoking by 100% (cessation) for three days. Primary outcomes were biological samples (carbon monoxide, urinary nicotine and cotinine). Participants also provided real-time reports of product use, craving, and withdrawal symptoms using a smartphone app. Dual users did not smoke fewer cigarettes than smoke-only participants during ad lib periods, but quadrupled their use of e-cigarettes during smoking reduction periods. Dual users were significantly more likely to maintain 100% reduction (97.1% vs. 81.2%). Amongst women, dual use was associated with higher nicotine levels and withdrawal suppression. Among a group of experienced dual users, e-cigarettes helped maintain smoking reduction and reduced some withdrawal symptoms, although both withdrawal symptoms and nicotine levels varied as a function of gender. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Acute electronic cigarette use: nicotine delivery and subjective effects in regular users.

PubMed

Dawkins, Lynne; Corcoran, Olivia

2014-01-01

Electronic cigarettes are becoming increasingly popular among smokers worldwide. Commonly reported reasons for use include the following: to quit smoking, to avoid relapse, to reduce urge to smoke, or as a perceived lower-risk alternative to smoking. Few studies, however, have explored whether electronic cigarettes (e-cigarettes) deliver measurable levels of nicotine to the blood. This study aims to explore in experienced users the effect of using an 18-mg/ml nicotine first-generation e-cigarette on blood nicotine, tobacco withdrawal symptoms, and urge to smoke. Fourteen regular e-cigarette users (three females), who are abstinent from smoking and e-cigarette use for 12 h, each completed a 2.5 h testing session. Blood was sampled, and questionnaires were completed (tobacco-related withdrawal symptoms, urge to smoke, positive and negative subjective effects) at four stages: baseline, 10 puffs, 60 min of ad lib use and a 60-min rest period. Complete sets of blood were obtained from seven participants. Plasma nicotine concentration rose significantly from a mean of 0.74 ng/ml at baseline to 6.77 ng/ml 10 min after 10 puffs, reaching a mean maximum of 13.91 ng/ml by the end of the ad lib puffing period. Tobacco-related withdrawal symptoms and urge to smoke were significantly reduced; direct positive effects were strongly endorsed, and there was very low reporting of adverse effects. These findings demonstrate reliable blood nicotine delivery after the acute use of this brand/model of e-cigarette in a sample of regular users. Future studies might usefully quantify nicotine delivery in relation to inhalation technique and the relationship with successful smoking cessation/harm reduction.

The effect of functional groups on reduction and activation of quinone bioreductive agents by DT-diaphorase.

PubMed

Fourie, Jeanne; Oleschuk, Curtis J; Guziec, Frank; Guziec, Lynn; Fiterman, Derek J; Monterrosa, Cielo; Begleiter, Asher

2002-02-01

Bioreductive antitumor agents are an important class of anticancer drugs that include the clinically used drug, mitomycin C, and new agents such as EO9 and tirapazamine that have recently been tested in clinical trials. These agents require activation by reductive enzymes such as DT-diaphorase or NADPH:cytochrome P450 reductase. A major focus for improving cancer chemotherapy has been to increase the selectivity and targeting of antitumor drugs to tumor cells. Bioreductive antitumor agents are ideally suited to improving tumor selectivity by an enzyme-directed approach to tumor targeting. However, none of the bioreductive agents developed to date has been specific for activation by a single reductive enzyme. This is in part due to a lack of knowledge about structural factors that confer selectivity for activation by reductive enzymes. The purpose of this study was to investigate the ability of specific functional groups to modify reduction and activation of quinone bioreductive agents by DT-diaphorase. We used a series of model benzoquinone mustard (BM) bioreductive agents and compared the parent compound BM to MBM, which has a strong electron-donating methoxy group, MeBM, which has a weaker electron-donating methyl group, CBM, which has an electron-withdrawing chloro group, and PBM and its structural isomer, meta-PBM (m-PBM), which both have sterically bulky benzene rings attached to the quinone moiety. We determined the rate of reduction of these agents by purified human DT-diaphorase under hypoxic and aerobic conditions. We also measured the cytotoxic activity of these agents in human tumor cell lines with and without the DT-diaphorase inhibitor, dicoumarol. Under hypoxic conditions in vitro, the t(1/2) values for reduction of the analogs by purified DT-diaphorase were 4, 6, 8, 9, 10 and 21 min for BM, MeBM, CBM, MBM, PBM and m-PBM, respectively. Under aerobic conditions the rank order of redox cycling after two-electron reduction by DT-diaphorase was MBM > MeBM > BM approximately CBM approximately PBM approximately m-PBM. The rate of reduction by DT-diaphorase of HBM, a non-alkylating analog of BM, was similar to that of BM under hypoxic conditions, and the rate of redox cycling under aerobic conditions was comparable to that of BM, suggesting that structural changes to the cytotoxic group of these BMs do not affect DT-diaphorase-mediated reduction and redox cycling potential. MBM, MeBM and PBM were more toxic than BM in the NCI-H661 human non-small-cell lung cancer cells and SK-MEL-28 human melanoma cells, while CBM displayed significantly increased cytotoxic activity compared to BM only in the NCI H661 cells. m-PBM had similar cytotoxic activity compared with BM in both cell lines. These cell lines have moderate to high levels of DT-diaphorase activity. When cells were pretreated with the DT-diaphorase inhibitor, dicoumarol, the cytotoxic activity of BM increased while that of MBM decreased in both cell lines, suggesting that BM was inactivated by DT-diaphorase while MBM was activated by this enzyme. Pretreatment of the SK-MEL-28 melanoma cells with dicoumarol resulted in an increased cytotoxic activity of MeBM, but pretreatment of the NCI-H661 cells did not affect the cytotoxicity of MeBM. This suggests, that similar to the results with BM, DT-diaphorase is an inactivating enzyme for MeBM in the SK-MEL-28 cell line. Dicoumarol had no significant effect on the cytotoxicity of CBM, PBM or m-PBM in both cell lines. These studies demonstrated that functional groups can significantly affect the reduction and activation of bioreductive agents by DT-diaphorase. All the functional groups decreased the rate of reduction of the quinone group by DT-diaphorase. Since MeBM and MBM, with electron-donating functional groups, and CBM with an electron-withdrawing functional group had similar half-lives of reduction by DT-diaphorase, steric rather than electronic effects of the functional groups appear to be more important for modifying the rate of reduction by DT-diaphorase. Steric effects on reduction by DT-diaphorase were also influenced by the position of the functional group on the quinone ring moiety, as the reduction of m-PBM was much slower than the reduction of PBM. The electron-donating methoxy and methyl functional groups increased the ability of the reduced products of MBM and MeBM to undergo redox cycling. DT-diaphorase appeared to be an activating enzyme for MBM. This may have resulted in part from increased formation of reactive oxygen species resulting from the increased redox cycling by MBM. In contrast, DT-diaphorase was an inactivating enzyme for BM, and for MeBM in the SK-MEL-28 melanoma cells, possibly because the hydroquinone product of BM and MeBM may be less cytotoxic than the semiquinone produced by one-electron reduction by NADPH:cytochrome P450 reductase.

The utility of bispectral index monitoring for prevention of rocuronium-induced withdrawal movement in children

PubMed Central

Lim, Byung Gun; Lee, Il Ok; Kim, Young Sung; Won, Young Ju; Kim, Heezoo; Kong, Myoung Hoon

2017-01-01

Abstract Background: This study was designed to determine whether a deep hypnotic state with a bispectral index (BIS) value less than 40 could alleviate withdrawal movement (WM) upon rocuronium injection during anesthesia induction in children. Methods: Finally, 135 healthy children (3–12 years) scheduled for minor elective surgery were studied. Without premedication, anesthesia was induced with thiopental sodium 5 mg/kg. Patients were randomized into 2 groups (control vs experimental) and then by virtue of rocuronium injection time, patients in the experimental group were allocated into 2 groups, as follows: in the control group (group C; n = 45), rocuronium 0.6 mg/kg was administered at the loss of eyelash reflex; in the 1st experimental group, rocuronium 0.6 mg/kg was administered when BIS fell to less than 40 (group T; n = 45); however, if BIS did not fall below 40 after thiopental sodium administration, manual ventilation was provided with oxygen 6 L/minute using sevoflurane 8% and then rocuronium was administered when BIS fell below 40 (the 2nd experimental group, group S; n = 45). Rocuronium-induced WM was evaluated using a 4-point scale (no movement; movement/withdrawal involving the arm only; generalized response, with movement/withdrawal of more than 1 extremity, but no requirement for restraint of the body; and generalized response which required restraint of the body and caused coughing or breath-holding). Results: No significant differences were found among the groups for patient characteristics including age, sex, height, and location of venous cannula. However, body weight, height, and body mass index in group S were all smaller than those in group T. The incidence of WM caused by rocuronium was 100% in group C, 95.6% in group T, and 80% in group S, and was significantly lower in group S than in group C. The grade of WM was 3.7 ± 0.6 in group C, 3.2 ± 0.9 in group T, and 2.6 ± 1.0 in group S. It was significantly lower in group T than in group C and significantly lower in group S than in groups C and T. Conclusion: The confirmation of a deep hypnotic state with BIS values lower than 40 using BIS monitoring can reduce the grade of rocuronium-induced WMs during anesthesia induction using thiopental sodium or sevoflurane in children. PMID:28079825

The utility of bispectral index monitoring for prevention of rocuronium-induced withdrawal movement in children: A randomized controlled trial.

PubMed

Lim, Byung Gun; Lee, Il Ok; Kim, Young Sung; Won, Young Ju; Kim, Heezoo; Kong, Myoung Hoon

2017-01-01

This study was designed to determine whether a deep hypnotic state with a bispectral index (BIS) value less than 40 could alleviate withdrawal movement (WM) upon rocuronium injection during anesthesia induction in children. Finally, 135 healthy children (3-12 years) scheduled for minor elective surgery were studied. Without premedication, anesthesia was induced with thiopental sodium 5 mg/kg. Patients were randomized into 2 groups (control vs experimental) and then by virtue of rocuronium injection time, patients in the experimental group were allocated into 2 groups, as follows: in the control group (group C; n = 45), rocuronium 0.6 mg/kg was administered at the loss of eyelash reflex; in the 1st experimental group, rocuronium 0.6 mg/kg was administered when BIS fell to less than 40 (group T; n = 45); however, if BIS did not fall below 40 after thiopental sodium administration, manual ventilation was provided with oxygen 6 L/minute using sevoflurane 8% and then rocuronium was administered when BIS fell below 40 (the 2nd experimental group, group S; n = 45). Rocuronium-induced WM was evaluated using a 4-point scale (no movement; movement/withdrawal involving the arm only; generalized response, with movement/withdrawal of more than 1 extremity, but no requirement for restraint of the body; and generalized response which required restraint of the body and caused coughing or breath-holding). No significant differences were found among the groups for patient characteristics including age, sex, height, and location of venous cannula. However, body weight, height, and body mass index in group S were all smaller than those in group T. The incidence of WM caused by rocuronium was 100% in group C, 95.6% in group T, and 80% in group S, and was significantly lower in group S than in group C. The grade of WM was 3.7 ± 0.6 in group C, 3.2 ± 0.9 in group T, and 2.6 ± 1.0 in group S. It was significantly lower in group T than in group C and significantly lower in group S than in groups C and T. The confirmation of a deep hypnotic state with BIS values lower than 40 using BIS monitoring can reduce the grade of rocuronium-induced WMs during anesthesia induction using thiopental sodium or sevoflurane in children.

Molecular design of cage iron(II) and cobalt(II,III) complexes with a second fluorine-enriched superhydrophobic shell.

PubMed

Belov, Alexander S; Zelinskii, Genrikh E; Varzatskii, Oleg A; Belaya, Irina G; Vologzhanina, Anna V; Dolganov, Alexander V; Novikov, Valentin V; Voloshin, Yan Z

2015-02-28

Pentafluorophenylboron-capped iron and cobalt(II) hexachloroclathrochelate precursors were obtained by the one-pot template condensation of dichloroglyoxime with pentafluorophenylboronic acid on iron and cobalt(II) ions under vigorous reaction conditions in trifluoroacetic acid media. These reactive precursors easily undergo nucleophilic substitution with (per)fluoroarylthiolate anions, giving (per)fluoroarylsulfide macrobicyclic complexes with encapsulated iron and cobalt(II) ions; nucleophilic substitution of the cobalt(II) hexachloroclathrochelate precursor with a pentafluorophenylsulfide anion gave the target hexasulfide monoclathrochelate and the mixed-valence Co(III)Co(II)Co(III) bis-clathrochelate as a side product. The complexes obtained were characterized using elemental analysis, MALDI-TOF mass spectrometry, IR, UV-Vis, (57)Fe Mössbauer (for the X-rayed iron complexes), (1)H, (11)B, (13)C and (19)F NMR spectroscopies and by X-ray diffraction; their redox and electrocatalytic behaviors were studied using cyclic voltammetry and gas chromatography. As can be seen from the single-crystal X-ray diffraction data, the second superhydrophobic shell of such caged metal ions is formed by fluorine atoms of both the apical and ribbed (per)fluoroaryl peripheral groups. The main bond distances and chelate N=C-C=N angles in their molecules are similar, but rotational elongation (contraction) along the molecular C3-pseudoaxes, accompanied by changes in the geometry of the corresponding MN6-coordination polyhedra from a trigonal prism to a trigonal antiprism, allowed encapsulating Fe(2+), Co(2+) and Co(3+) ions. The nature of an encapsulated metal ion and its oxidation state affect the M-N bond lengths, and, for cobalt(ii) clathrochelate with an electronic configuration d(7) the Jahn-Teller structural effect is observed as an alternation of the Co-N distances. Pentafluorophenylboron-capped hexachloroclathrochelate precursors, giving stable catalytically active metal(I)-containing intermediates due to the electron-withdrawing effect of their six ribbed chlorine substituents, were found to show moderate electrocatalytic activity in a 2H(+)/H2 hydrogen-forming reaction. In the case of their ribbed-functionalized sulfide derivatives, the strong electron-withdrawing (per)fluoroaryl groups do not stabilize the reduced electrocatalytically active metal(i)-containing species as their mesomeric effect is absent or substantially decreased by steric hindrances between them.

Novel High Efficient Organic Photovoltaic Materials: Final Summary of Research

NASA Technical Reports Server (NTRS)

Sun, Sam

2002-01-01

The objectives and goals of this project were to investigate and develop high efficient, lightweight, and cost effective materials for potential photovoltaic applications, such as solar energy conversion or photo detector devices. Specifically, as described in the original project proposal, the target material to be developed was a block copolymer system containing an electron donating (or p-type) conjugated polymer block coupled to an electron withdrawing (or n-type) conjugated polymer block through a non-conjugated bridge unit. Due to several special requirements of the targeted block copolymer systems, such as electron donating and withdrawing substituents, conjugated block structures, processing requirement, stability requirement, size controllability, phase separation and self ordering requirement, etc., many traditional or commonly used block copolymer synthetic schemes are not suitable for this system. Therefore, the investigation and development of applicable and effective synthetic protocols became the most critical and challenging part of this project. During the entire project period, and despite the lack of a proposed synthetic polymer postdoctoral research associate due to severe shortage of qualified personnel in the field, several important accomplishments were achieved in this project and are briefly listed and elaborated. A more detailed research and experimental data is listed in the Appendix.

Effectiveness of the electronic cigarette: An eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints.

PubMed

Adriaens, Karolien; Van Gucht, Dinska; Declerck, Paul; Baeyens, Frank

2014-10-29

Smoking reduction remains a pivotal issue in public health policy, but quit rates obtained with traditional quit-smoking therapies remain disappointingly low. Tobacco Harm Reduction (THR), aiming at less harmful ways of consuming nicotine, may provide a more effective alternative. One promising candidate for THR are electronic cigarettes (e-cigs). The aim of this study was to investigate the efficacy of second-generation e-cigs both in terms of acute craving-reduction in the lab and in terms of smoking reduction and experienced benefits/complaints in an eight-month Randomized Controlled Trial (RCT). RCT with three arms. Participants (N = 48) unwilling to quit smoking were randomized into two e-cig groups and one control group. During three lab sessions (over two months) participants, who had been abstinent for four hours, vaped/smoked for five minutes, after which we monitored the effect on craving and withdrawal symptoms. eCO and saliva cotinine levels were also measured. In between lab sessions, participants in the e-cig groups could use e-cigs or smoke ad libitum, whereas the control group could only smoke. After the lab sessions, the control group also received an e-cig. The RCT included several questionnaires, which repeatedly monitored the effect of ad libitum e-cig use on the use of tobacco cigarettes and the experienced benefits/complaints up to six months after the last lab session. From the first lab session on, e-cig use after four hours of abstinence resulted in a reduction in cigarette craving which was of the same magnitude as when a cigarette was smoked, while eCO was unaffected. After two months, we observed that 34% of the e-cig groups had stopped smoking tobacco cigarettes, versus 0% of the control group. After five months, the e-cig groups demonstrated a total quit-rate of 37%, whereas the control group showed a quit rate of 38% three months after initiating e-cig use. At the end of the eight-month study, 19% of the e-cig groups and 25% of the control group were totally abstinent from smoking, while an overall reduction of 60% in the number of cigarettes smoked per day was observed (compared to intake). eCO levels decreased, whereas cotinine levels were the same in all groups at each moment of measurement. Reported benefits far outweighed the reported complaints. In a series of controlled lab sessions with e-cig naïve tobacco smokers, second generation e-cigs were shown to be immediately and highly effective in reducing abstinence induced cigarette craving and withdrawal symptoms, while not resulting in increases in eCO. Remarkable (>50 pc) eight-month reductions in, or complete abstinence from tobacco smoking was achieved with the e-cig in almost half (44%) of the participants.

Self-Assembly of Cis-Configured Squaraine Dyes at the TiO2-Dye Interface: Far-Red Active Dyes for Dye-Sensitized Solar Cells.

PubMed

Punitharasu, Vellimalai; Mele Kavungathodi, Munavvar Fairoos; Nithyanandhan, Jayaraj

2018-05-16

To synergize both steric and electronic factors in designing the dyes for dye-sensitized solar cells, a series of cis-configured unsymmetrical squaraine dyes P11-P15 with suitably functionalized alkyl groups and squaric acid units containing the electron-withdrawing groups were synthesized, respectively. These dyes capture the importance of (i) the effect and position of branched alkyl groups, (ii) mono- and di-anchoring groups containing dyes, and (iii) further appending the alkyl groups through the cyanoester vinyl unit on the central squaric acid units of D-A-D-based cis-configured squaraine dyes. All the above factors govern the controlled self-assembly of the dyes on the TiO 2 surface which helps to broaden the absorption profile of the dyes with an increased energy-harvesting process. With respect to the position of the branched alkyl groups, dye P11 with the sp 3 -C and N-alkyl groups away from the TiO 2 surface showed a better device efficiency of 5.98% ( J sc of 14.46 mA cm -2 , V oc of 0.576 V, and ff of 71.8%) than its positional isomer P12 with 3.45% ( J sc of 8.78 mA cm -2 , V oc of 0.554 V, and ff of 70.9%). However, with respect to the dyes containing mono- and di-anchoring groups, P13 with two anchoring units exhibited a superior device performance of 7.58% ( J sc of 17.12 mA cm -2 , V oc of 0.618 V, and ff of 71.7%) in the presence of optically transparent co-adsorbent CDCA (3α,7α-dihydroxy-5β-cholanic acid) than dyes P11 and P12.

Tobacco Withdrawal Amongst African American, Hispanic, and White Smokers.

PubMed

Bello, Mariel S; Pang, Raina D; Cropsey, Karen L; Zvolensky, Michael J; Reitzel, Lorraine R; Huh, Jimi; Leventhal, Adam M

2016-06-01

Persistent tobacco use among racial and ethnic minority populations in the United States is a critical public health concern. Yet, potential sources of racial/ethnic disparities in tobacco use remain unclear. The present study examined racial/ethnic differences in tobacco withdrawal-a clinically-relevant underpinning of tobacco use that has received sparse attention in the disparities literature-utilizing a controlled laboratory design. Daily smokers (non-Hispanic African American [n = 178], non-Hispanic white [n = 118], and Hispanic [n = 28]) attended two counterbalanced sessions (non-abstinent vs. 16-hour abstinent). At both sessions, self-report measures of urge, nicotine withdrawal, and affect were administered and performance on an objective behavioral task that assessed motivation to reinstate smoking was recorded. Abstinence-induced changes (abstinent scores vs. non-abstinent scores) were analyzed as a function of race/ethnicity. Non-Hispanic African American smokers reported greater abstinence-induced declines in several positive affect states in comparison to other racial/ethnic groups. Relative to Hispanic smokers, non-Hispanic African American and non-Hispanic white smokers displayed larger abstinence-provoked increases in urges to smoke. No racial/ethnic differences were detected for a composite measure of nicotine withdrawal symptomatology, negative affect states, and motivation to reinstate smoking behavior. These results suggest qualitative differences in the expression of some components of tobacco withdrawal across three racial/ethnic groups. This research helps shed light on bio-behavioral sources of tobacco-related health disparities, informs the application of smoking cessation interventions across racial/ethnic groups, and may ultimately aid the overall effort towards reducing the public health burden of tobacco addiction in minority populations. The current study provides some initial evidence that there may be qualitative differences in the types of tobacco withdrawal symptoms experienced among non-Hispanic African American, Hispanic, and non-Hispanic white smokers. Extending this line of inquiry may elucidate mechanisms involved in tobacco-related health disparities and ultimately aid in reducing the public health burden of smoking in racial/ethnic minority populations. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Degradation of phenolic compounds with hydrogen peroxide catalyzed by enzyme from Serratia marcescens AB 90027.

PubMed

Yao, Ri-Sheng; Sun, Min; Wang, Chun-Ling; Deng, Sheng-Song

2006-09-01

In this paper, the degradation of phenolic compounds using hydrogen peroxide as oxidizer and the enzyme extract from Serratia marcescens AB 90027 as catalyst was reported. With such an enzyme/H2O2 combination treatment, a high chemical oxygen demand (COD) removal efficiency was achieved, e.g., degradation of hydroquinone exceeded 96%. From UV-visible and IR spectra, the degradation mechanisms were judged as a process of phenyl ring cleavage. HPLC analysis shows that in the degradation p-benzoquinone, maleic acid and oxalic acid were formed as intermediates and that they were ultimately converted to CO2 and H2O. With the enzyme/H2O2 treatment, vanillin, hydroquinone, catechol, o-aminophenol, p-aminophenol, phloroglucinol and p-hydroxybenzaldehyde were readily degraded, whereas the degradation of phenol, salicylic acid, resorcinol, p-cholorophenol and p-nitrophenol were limited. Their degradability was closely related to the properties and positions of their side chain groups. Electron-donating groups, such as -OH, -NH2 and -OCH3 enhanced the degradation, whereas electron-withdrawing groups, such as -NO2, -Cl and -COOH, had a negative effect on the degradation of these compounds in the presence of enzyme/H2O2. Compounds with -OH at ortho and para positions were more readily degraded than those with -OH at meta positions.

Reasons for not using ecstasy: a qualitative study of non-users, ex-light users and ex-moderate users

PubMed Central

2012-01-01

Background Although ecstasy is often consumed in the electronic music scene, not everyone with the opportunity to use it chooses to do so. The objective of this study was to understand the reasons for non-use or the cessation of use, which could provide information for public health interventions. Methods A qualitative reference method was used. Our “snowball” sample group consisted of 53 people who were split into three subgroups: non-users (NU, n = 23), ex-light users (EX-L, n = 12) and ex-moderate users (EX-M, n = 18). Individual, semi-structured interviews were conducted, transcribed and subjected to content analysis with the aid of NVivo8. Results Adverse health effects and personal values were given as reasons for non-use in the three groups. Non-users (NU) and ex-light users (EX-L) provided reasons that included fear of possible effects as well as moral, family and religious objections. Ex-moderate users (EX-M) cited reasons related to health complications and concomitant withdrawal from the electronic music scene. However, most of the ex-moderate users did not rule out the possibility of future use. Conclusions Potential effects and undesirable consequences appear to guide the decisions within the different groups. Prevention might target these motivations. Individuals who have used ecstasy indicate that social and environmental factors are the most important factors. PMID:22583984

How to Submit a Risk Management Plan (RMP) to EPA

EPA Pesticide Factsheets

RMP*eSubmit software is the only way to submit RMPs. After you have prepared your plan using RMP*eSubmit, you may also re-submit, correct, or withdraw an RMP. Another electronic tool, RMP*Comp, performs the required off-site consequence analysis.

Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

PubMed

Greenberg, G D; Huang, L C; Spence, S E; Schlumbohm, J P; Metten, P; Ozburn, A R; Crabbe, J C

2016-04-01

Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice. Published by Elsevier B.V.

Evidence-based guidelines for anti-allergic drug withdrawal times before allergen-specific intradermal and IgE serological tests in dogs.

PubMed

Olivry, Thierry; Saridomichelakis, Manolis

2013-04-01

Anti-allergic drugs (e.g. antihistamines, glucocorticoids and ciclosporin) are often administered to dogs with atopic dermatitis to relieve pruritus and skin lesions. Allergen-specific intradermal tests (IDT) and allergen-specific IgE serological (ASIS) tests are used to characterize the allergens to which dogs are hypersensitive. Anti-allergic drugs have the potential to influence the results or interpretation of these tests. To provide evidence-based recommendations for anti-allergic drug withdrawal times before IDT and ASIS tests. Three citation databases and abstracts from international meetings were searched for relevant studies. Studies were grouped based on similar interventions and types of tests. Withdrawal times for each type of drug and test were then extrapolated from the study results. Before the assessment of immediate reactions to IDT, proposed optimal withdrawal times for antihistamines, oral glucocorticoids, topical/otic glucocorticoids and ciclosporin are 7, 14, 14 and 0 days, respectively. Studies have provided no evidence for drug withdrawal prior to ASIS tests for oral ciclosporin or prednisone/prednisolone. Owing to a lack of studies, recommendations for withdrawal times before ASIS tests cannot be made for topical glucocorticoids and antihistamines. These proposed withdrawal times are based on the existing evidence at the end of 2011. Care must be taken before extrapolating the suggested withdrawal times to other species, higher dosages, different formulations and/or durations of administration of tested drugs, as well as to other medications from the same category. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation.

PubMed

Muelken, Peter; Schmidt, Clare E; Shelley, David; Tally, Laura; Harris, Andrew C

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e.g., anxiety-like behavior, somatic signs), may be useful for understanding the development of the nicotine withdrawal syndrome.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

PubMed Central

Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e.g., anxiety-like behavior, somatic signs), may be useful for understanding the development of the nicotine withdrawal syndrome. PMID:26658557

Comparing the effect of buprenorphine and methadone in the reduction of methamphetamine craving: a randomized clinical trial.

PubMed

Ahmadi, Jamshid; Razeghian Jahromi, Leila

2017-06-06

We sought to test the effectiveness of methadone and buprenorphine in the treatment of methamphetamine withdrawal craving over a 17-day treatment period. Patients were randomized into one of two groups. The study sample comprised 40 male subjects dependent on methamphetamine who met criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, for methamphetamine dependence and withdrawal and were seeking treatment. Furthermore, they should have a history of daily methamphetamine use for at least 6 months and should have discontinued their use just before starting the protocol. Patients received 40 mg of methadone or 8 mg of buprenorphine per day and were treated in an inpatient psychiatric hospital. We used methamphetamine craving score, negative urine drug screening test (thin-layer chromatography) during the study, and retention in treatment. All 40 patients completed the study. Both drugs were effective in decreasing methamphetamine craving during methamphetamine withdrawal. Reduction of craving in the buprenorphine group was significantly more than in the methadone group (P < 0.05). The results favor the efficacy and safety of buprenorphine as a short-term treatment for methamphetamine withdrawal craving. We should mention that it is to be expected that craving declines over time without any medication. Therefore, the conclusion may not be that methadone and buprenorphine both reduce the craving. Because buprenorphine is superior to methadone, only buprenorphine surely reduces craving. Iranian Registry of Clinical Trials identifier: IRCT2015112125160N1 . Registered on 4 June 2016.

Stories of Hell and Healing: Internet Users' Construction of Benzodiazepine Distress and Withdrawal.

PubMed

Fixsen, Alison M; Ridge, Damien

2017-11-01

Benzodiazepines are a group of drugs used mainly as sedatives, hypnotics, antiepileptics, and muscle relaxants. Consumption is recommended for 2 to 4 weeks only, due to fast onset of dependency and potentially distressing withdrawal symptoms. Few peer-review studies have drawn on the user experiences and language to appreciate firsthand experiences of benzodiazepine withdrawal or discontinuation syndrome. We looked extensively at patient stories of benzodiazepine withdrawal and recovery on Internet support sites and YouTube. Our analysis indicated that users employ rich metaphors to portray the psychologically disturbing and protracted nature of their suffering. We identified seven major themes: hell and isolation, anxiety and depression, alienation, physical distress, anger and remorse, waves and windows, and healing and renewal. By posting success stories, ex-users make known that "healing" can be a long, unpredictable process, but distress does lessen, and recovery can happen.

Emplotting Hikikomori: Japanese Parents' Narratives of Social Withdrawal.

PubMed

Rubinstein, Ellen

2016-12-01

Hikikomori, often glossed as "social withdrawal," emerged as a sociomedical condition among Japanese youth at the end of the twentieth century, and it continues to fascinate and concern the public. Explanatory frameworks for hikikomori abound, with different stakeholders attributing it to individual psychopathology, poor parenting, and/or a lack of social support structures. This article takes an interpretive approach to hikikomori by exploring parents' narrative constructions of hikikomori children in support group meetings and in-depth interviews. I argue that some parents were able to find hope in hikikomori by 'emplotting' their children's experiences into a larger narrative about onset, withdrawal, and recovery, which helped them remain invested in the present by maintaining a sense of possibility about the future. Contrary to literature that examines hikikomori as an epidemic of isolated individuals, I demonstrate how parents play a key role in hikikomori through meaning-making activities that have the potential to shape their children's experiences of withdrawal.

Changes in serum biochemical factors associated with opium addiction after addiction desertion.

PubMed

Afarinesh, Mohammad Reza; Haghpanah, Tahereh; Divsalar, Kouros; Dehyadegary, Elham; Shaikh-Aleslami, Azar; Mahmoodi, Majid

2014-01-01

The long time use of opium has some effects on serums biochemical factors, the determination of this variation is a new approach in understanding off addiction and relive of drug abuser health. Hence in this study, these indicators in person who were withdrawing of opium have been studied. In this cross-sectional study bloods biochemical factors such as fasting blood sugar (FBS), sodium (Na), calcium (Ca), uric acid (UA), blood urea nitrogen (BUN), creatinine, cholesterol, total protein, and fibrinogen in three groups serum were studied: (1) Who had been permanent opium users more than 2 years (case). (2) Dependent person who has taken one month addiction withdrawal course (control). (3) A healthy group that had been demographically similar to the other groups. According to these study findings, FBS serum level in the case group is lower than control group. Serum level of Na, creatinine, and blood triglyceride (TG) in case study are higher than group control. Concentration of potassium, Ca, UA, BUN, cholesterol, total serum protein, fibrinogen, and thrombin time in case study and group control showed no significant difference. Also, in withdrawing case serum level of Na, Ca, UA, BUN, creatinine, and TG significantly increase and thrombin time decrease. According to this study not only the longtime use of opium but also opium with drawerin opium dependent people can change their serum biochemical factors. So recognition, treatment, and prevention of this change could be a new step in improving of health and condition of patients.

Group hypnosis vs. relaxation for smoking cessation in adults: a cluster-randomised controlled trial.

PubMed

Dickson-Spillmann, Maria; Haug, Severin; Schaub, Michael P

2013-12-23

Despite the popularity of hypnotherapy for smoking cessation, the efficacy of this method is unclear. We aimed to investigate the efficacy of a single-session of group hypnotherapy for smoking cessation compared to relaxation in Swiss adult smokers. This was a cluster-randomised, parallel-group, controlled trial. A single session of hypnosis or relaxation for smoking cessation was delivered to groups of smokers (median size = 11). Participants were 223 smokers consuming ≥ 5 cigarettes per day, willing to quit and not using cessation aids (47.1% females, M = 37.5 years [SD = 11.8], 86.1% Swiss). Nicotine withdrawal, smoking abstinence self-efficacy, and adverse reactions were assessed at a 2-week follow-up. The main outcome, self-reported 30-day point prevalence of smoking abstinence, was assessed at a 6-month follow up. Abstinence was validated through salivary analysis. Secondary outcomes included number of cigarettes smoked per day, smoking abstinence self-efficacy, and nicotine withdrawal. At the 6-month follow up, 14.7% in the hypnosis group and 17.8% in the relaxation group were abstinent. The intervention had no effect on smoking status (p = .73) or on the number of cigarettes smoked per day (p = .56). Smoking abstinence self-efficacy did not differ between the interventions (p = .14) at the 2-week follow-up, but non-smokers in the hypnosis group experienced reduced withdrawal (p = .02). Both interventions produced few adverse reactions (p = .81). A single session of group hypnotherapy does not appear to be more effective for smoking cessation than a group relaxation session. Current Controlled Trials ISRCTN72839675.

p -Carborane Conjugation in Radical Anions of Cage–Cage and Cage–Phenyl Compounds

DOE PAGES

Cook, Andrew R.; Valášek, Michal; Funston, Alison M.; ...

2017-12-14

Optical electron transfer (intervalence) transitions in radical anions of p-carborane oligomers attest to delocalization of electrons between two p-carboranes cages or a p-carborane and a phenyl ring. Oligomers of the 12 vertex p-carborane (C 2B 10H 12) cage, [12], with up to 3 cages were synthesized, as well as p-carboranes with one or two trimethylsilylphenyl groups, [6], attached to the carbon termini. Pulse radiolysis in tetrahydrofuran produced radical anions, determined redox potentials by equilibria and measured their absorption spectra. Density functional theory computations provided critical insight into the optical electron transfer bands and electron delocalization. One case, [6–12–6], showed bothmore » Robin–Day class II and III transitions. The class III transition resulted from a fully delocalized excess electron across both benzene rings and the central p-carborane, with an electronic coupling H ab = 0.46 eV between the cage and either benzene. This unprecedented finding shows that p-carborane bridges are not simply electron withdrawing insulators. In other cases with more than ~1/2 of the excess electron localized on a [12], large cage distortions were triggered, producing a partially open cage with a nido-like structure. This resulted in class II transitions with similar Hab but massive reorganization energies. The computations also predicted delocalization in radical cations, but complexities in cation formation allowed only tentative experimental support of the predictions. Thus, the results with anions provide clear evidence for carborane conjugation that might be exploited in molecular wire materials, which are classically composed of all π-conjugated molecules.« less

p -Carborane Conjugation in Radical Anions of Cage–Cage and Cage–Phenyl Compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, Andrew R.; Valášek, Michal; Funston, Alison M.

Optical electron transfer (intervalence) transitions in radical anions of p-carborane oligomers attest to delocalization of electrons between two p-carboranes cages or a p-carborane and a phenyl ring. Oligomers of the 12 vertex p-carborane (C 2B 10H 12) cage, [12], with up to 3 cages were synthesized, as well as p-carboranes with one or two trimethylsilylphenyl groups, [6], attached to the carbon termini. Pulse radiolysis in tetrahydrofuran produced radical anions, determined redox potentials by equilibria and measured their absorption spectra. Density functional theory computations provided critical insight into the optical electron transfer bands and electron delocalization. One case, [6–12–6], showed bothmore » Robin–Day class II and III transitions. The class III transition resulted from a fully delocalized excess electron across both benzene rings and the central p-carborane, with an electronic coupling H ab = 0.46 eV between the cage and either benzene. This unprecedented finding shows that p-carborane bridges are not simply electron withdrawing insulators. In other cases with more than ~1/2 of the excess electron localized on a [12], large cage distortions were triggered, producing a partially open cage with a nido-like structure. This resulted in class II transitions with similar Hab but massive reorganization energies. The computations also predicted delocalization in radical cations, but complexities in cation formation allowed only tentative experimental support of the predictions. Thus, the results with anions provide clear evidence for carborane conjugation that might be exploited in molecular wire materials, which are classically composed of all π-conjugated molecules.« less

Maternal education, dental visits and age of pacifier withdrawal: pediatric dentist role in malocclusion prevention.

PubMed

Pérez-Suárez, V; Carrillo-Diaz, M; Crego, A; Romero, M

2013-01-01

Although discouraged, pacifier usage is widespread and often practiced beyond two years of age. The current study explored the effects of maternal education and dental visits on the age of pacifier withdrawal. The dental histories of 213 children (53.1% male) attending a primary school in Madrid were obtained along with maternal education level and age at pacifier withdrawal. Data were analyzed by using independent samples t-test, one-way ANOVA two-way ANOVA and a complementary non-parametric approach was also used. There was a significant effect of maternal education on the age of pacifier withdrawal; the higher the maternal education, the younger the age of withdrawal. The frequency of dental visits influenced the relationship between maternal education and the age of pacifier withdrawal. Dental visits considerably shortened pacifier use among children with low- and medium-educated mothers. Pediatric dentists play a critical role in the correction of unhealthy oral habits such as prolonged pacifier use. The educational component of pediatric dentistry could reverse the lack of knowledge or misinformation among high-risk groups (e.g. low maternal education). As a consequence, we recommend that children start dental visits at an early age and maintain visits with a high frequency.

Cost effectiveness of withdrawal of fall-risk-increasing drugs in geriatric outpatients.

PubMed

van der Velde, Nathalie; Meerding, Willen Jan; Looman, Caspar W; Pols, Huibert A P; van der Cammen, Tischa J M

2008-01-01

Withdrawal of fall-risk-increasing drugs has been proven to be effective in older persons. However, given the enormous rise in healthcare costs in recent decades, the effect of such withdrawals on healthcare costs also needs to be considered. Within a common geriatric outpatient population, patients with a history of falls were assessed for falls risk (n = 139). Fall-risk-increasing drugs were withdrawn when appropriate (n = 75). All participants had a 2-month follow-up for fall incidents. The number of prevented falls was calculated using a loglinear regression model. The savings on health expenditures as a result of prevented injuries (estimated from a literature review) and reduced consumption of pharmaceuticals were compared with the intervention costs. After adjustment for confounders, drug withdrawal resulted in a falls risk reduction of 0.89 (95% CI 0.33, 0.98) per patient compared with the non-withdrawal group. Net cost savings were euro1691 (95% CI 662, 2181) per patient in the cohort. This resulted in a cost saving of euro491 (95% CI 465, 497) per prevented fall. Withdrawal of fall-risk-increasing drugs generates significant cost savings. Extrapolation of these findings to a national scale results in an estimated reduction of euro60 million in healthcare expenditures, that is, 15% of fall-related health costs.

Extended access to methamphetamine self-administration up-regulates dopamine transporter levels 72 hours after withdrawal in rats.

PubMed

D'Arcy, Christina; Luevano, Joe E; Miranda-Arango, Manuel; Pipkin, Joseph A; Jackson, Jonathan A; Castañeda, Eddie; Gosselink, Kristin L; O'Dell, Laura E

2016-01-01

Previous studies have demonstrated that there are persistent changes in dopamine systems following withdrawal from methamphetamine (METH). This study examined changes in striatal dopamine transporter (DAT), tyrosine hydroxylase (TH) and dopamine receptor 2 (D2) 72 h after withdrawal from METH intravenous self- administration (IVSA). Rats were given limited (1h) or extended (6h) access to METH IVSA (0.05 mg/kg/0.1 ml infusion) for 22 days. Controls did not receive METH IVSA. The rats given extended access to IVSA displayed higher METH intake during the first hour of drug access compared to rats given limited access. Extended access to METH also produced a concomitant increase in striatal DAT levels relative to drug-naïve controls. There were no changes in TH or D2 levels across groups. Previous studies have reported a decrease in striatal DAT levels during protracted periods (>7 days) of withdrawal from METH IVSA. This study extends previous work by showing an increase in striatal DAT protein expression during an earlier time point of withdrawal from this drug. These results are an important step toward understanding the dynamic changes in dopamine systems that occur during different time points of withdrawal from METH IVSA. Copyright © 2015 Elsevier B.V. All rights reserved.

Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

PubMed

Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

2013-03-01

Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Addiction in Extreme Sports: An Exploration of Withdrawal States in Rock Climbers

PubMed Central

Heirene, Robert M.; Shearer, David; Roderique-Davies, Gareth; Mellalieu, Stephen D.

2016-01-01

Background and aims Extreme sports athletes are often labeled “adrenaline junkies” by the media, implying they are addicted to their sport. Research suggests during abstinence these athletes may experience withdrawal states characteristic of individuals with an addiction (Celsi, Rose, & Leigh, 1993; Franken, Zijlstra, & Muris, 2006; Willig, 2008). Despite this notion, no research has directly explored withdrawal experiences of extreme sports athletes. Methods Using semi-structured interviews, we explored withdrawal experiences of high (n = 4) and average-ability (n = 4) male rock climbers during periods of abstinence. We investigated the psychological and behavioral aspects of withdrawal, including craving, anhedonia, and negative affect; and differences in the frequency and intensity of these states between groups. Results Deductive content analysis indicated support for each of the three categories of anhedonia, craving, and negative affect. Consistent with existing substance addiction literature, high-ability climbers recalled more frequent and intense craving states and negative affect during abstinence compared with average-ability climbers. No differences in anhedonic symptoms between high and average-ability participants were found. Conclusions Rock climbing athletes appear to experience withdrawal symptoms when abstinent from their sport comparable to individuals with substance and behavioral addictions. The implications of these findings and suggestions for future research are discussed. PMID:27348554

Synthesis, hydrolysis rates, supercomputer modeling, and antibacterial activity of bicyclic tetrahydropyridazinones.

PubMed

Jungheim, L N; Boyd, D B; Indelicato, J M; Pasini, C E; Preston, D A; Alborn, W E

1991-05-01

Bicyclic tetrahydropyridazinones, such as 13, where X are strongly electron-withdrawing groups, were synthesized to investigate their antibacterial activity. These delta-lactams are homologues of bicyclic pyrazolidinones 15, which were the first non-beta-lactam containing compounds reported to bind to penicillin-binding proteins (PBPs). The delta-lactam compounds exhibit poor antibacterial activity despite having reactivity comparable to the gamma-lactams. Molecular modeling based on semiempirical molecular orbital calculations on a Cray X-MP supercomputer, predicted that the reason for the inactivity is steric bulk hindering high affinity of the compounds to PBPs, as well as high conformational flexibility of the tetrahydropyridazinone ring hampering effective alignment of the molecule in the active site. Subsequent PBP binding experiments confirmed that this class of compound does not bind to PBPs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powers, Andrew R.; Ghiviriga, Ion; Abboud, Khalil A.

This report outlines the investigation of the iClick mechanism between gold(I)-azides and gold(I)-acetylides to yield digold triazolates. Isolation of digold triazolate complexes offer compelling support for the role of two copper(I) ions in CuAAC. In addition, a kinetic investigation reveals the reaction is first order in both Au(I)-N 3 and Au(I)-C≡C-R equivalent to C-R, thus second order overall. A Hammett plot with a ρ = 1.02(5) signifies electron-withdrawing groups accelerate the cycloaddition by facilitating the coordination of the second gold ion in a π-complex. Rate inhibition by the addition of free triphenylphosphine to the reaction indicates that ligand dissociation ismore » a prerequisite for the reaction. The mechanistic conclusions mirror those proposed for the CuAAC reaction.« less

15 CFR 335.5 - Licenses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... importer as suitable for use in making suits, suit-type jackets, or trousers under the appropriate Tariff... (Customs Form 7501). (f) A Licensee may only authorize an importer to import fabric under the license on... the entry summary or warehouse withdrawal for consumption (Customs Form 7501), or its electronic...

15 CFR 335.5 - Licenses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... importer as suitable for use in making suits, suit-type jackets, or trousers under the appropriate Tariff... (Customs Form 7501). (f) A Licensee may only authorize an importer to import fabric under the license on... the entry summary or warehouse withdrawal for consumption (Customs Form 7501), or its electronic...

15 CFR 335.5 - Licenses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... importer as suitable for use in making suits, suit-type jackets, or trousers under the appropriate Tariff... (Customs Form 7501). (f) A Licensee may only authorize an importer to import fabric under the license on... the entry summary or warehouse withdrawal for consumption (Customs Form 7501), or its electronic...

15 CFR 335.5 - Licenses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... importer as suitable for use in making suits, suit-type jackets, or trousers under the appropriate Tariff... (Customs Form 7501). (f) A Licensee may only authorize an importer to import fabric under the license on... the entry summary or warehouse withdrawal for consumption (Customs Form 7501), or its electronic...

Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain.

PubMed

Van Bockstaele, Elisabeth J; Qian, Yaping; Sterling, Robert C; Page, Michelle E

2008-05-15

The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone-precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pre-treatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional 4 h. At the end of the experiment, animals were transcardially perfused and the brains were removed for verification of probe placement. Low dose naltrexone pre-treatment significantly attenuated withdrawal-induced increases of extracellular norepinephrine in the BNST, with a smaller effect in the FC. These findings suggest that alterations in norepinephrine release associated with withdrawal may be attenuated in forebrain targets of noradrenergic brainstem neurons that may underlie reduced behavioral signs of withdrawal following low dose naltrexone administration.

One-pot, two-step desymmetrization of symmetrical benzils catalyzed by the methylsulfinyl (dimsyl) anion.

PubMed

Ragno, Daniele; Bortolini, Olga; Giovannini, Pier Paolo; Massi, Alessandro; Pacifico, Salvatore; Zaghi, Anna

2014-08-14

An operationally simple one-pot, two-step procedure for the desymmetrization of benzils is herein described. This consists in the chemoselective cross-benzoin reaction of symmetrical benzils with aromatic aldehydes catalyzed by the methyl sulfinyl (dimsyl) anion, followed by microwave-assisted oxidation of the resulting benzoylated benzoins with nitrate, avoiding the costly isolation procedure. Both electron-withdrawing and electron-donating substituents may be accommodated on the aromatic rings of the final unsymmetrical benzil.

Effect of thought suppression on desire to smoke and tobacco withdrawal symptoms.

PubMed

Erskine, James A K; Ussher, Michael; Cropley, Mark; Elgindi, Abdelaziz; Zaman, Manzir; Corlett, Bethan

2012-01-01

Suppressing smoking thoughts has been shown to result in elevated smoking. However, the effect of suppressing smoking thoughts on desire to smoke and withdrawal symptoms has not been investigated. We examined the effects of suppressing smoking thoughts on the subsequent desire to smoke and on tobacco withdrawal symptoms, relative to groups that were either thinking about anything they wished or actively thinking about smoking. A randomised experimental study compared the effects of three manipulations (suppressed smoking thoughts, expressed smoking thoughts and thoughts of anything they wished) on desire and withdrawal immediately after the manipulation and 5 and 10 min after. Suppressing smoking thoughts did not result in elevated subsequent desire to smoke, relative to the other manipulations. Suppressing smoking thoughts resulted in a significant elevation in hunger ratings, relative to the other manipulations, at all measurement times. There were no significant effects for the other withdrawal symptoms. Self-reported greater use of thought suppression in everyday life was significantly associated with greater desire to smoke at baseline and was associated with lower mindfulness scores. Laboratory-instructed suppression of smoking thoughts is associated with increased reports of hunger but did not lead to increases in other withdrawal symptoms or elevated desire to smoke. Reports of everyday use of thought suppression are associated with elevated desire to smoke at baseline. Further investigations need to assess the effect of suppressing smoking cravings, instead of general smoking thoughts, on desire to smoke and tobacco withdrawal.

Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to heroin seeking in rodents.

PubMed

de Guglielmo, Giordano; Kallupi, Marsida; Scuppa, Giulia; Demopulos, Gregory; Gaitanaris, George; Ciccocioppo, Roberto

2017-01-01

Relapse to opioids is often driven by the avoidance of the aversive states of opioid withdrawal. We recently demonstrated that activation of peroxisome proliferator-activated receptor gamma (PPARγ) by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. However, the role of PPARγ in withdrawal and other forms of relapse to heroin is unknown. To further address this issue, we investigated the role of PPARγ on the development and expression of morphine withdrawal in mice and the effect of pioglitazone on several forms of heroin relapse in rats. We induced physical dependence to morphine in mice by injecting morphine twice daily for 6 days. Withdrawal syndrome was precipitated on day 6 with an injection of naloxone. In addition, different groups of rats were trained to self-administer heroin and, after the extinction, the relapse was elicited by cues, priming, or stress. The effect of different doses of pioglitazone was tested on these different paradigms. Data show that chronic and acute administration of pioglitazone attenuates morphine withdrawal symptoms, and these effects are mediated by activation of PPARγ receptors. Activation of PPARγ by pioglitazone also abolishes yohimbine-induced reinstatement of heroin seeking and reduces heroin-induced reinstatement, while it does not affect cue-induced relapse. These findings provide new insights on the role of PPARγ on opioid dependence and suggest that pioglitazone may be useful for the treatment of opioid withdrawal in opioid-addicted individuals.

Water withdrawal and use in Maryland, 1992-93

USGS Publications Warehouse

Wheeler, J.C.

1997-01-01

During 1992, about 1,430 million gallons per day (Mgal/d) of freshwater was withdrawn from surface-water and ground-water sources in Maryland. Total freshwater withdrawals increased during 1993 to about 1,480 Mgal/d. Saline surface- water withdrawals for cooling condensers increased from about 5,350 Mgal/d during 1992 to 5,840 Mgal/d during 1993. During 1992-93, most freshwater withdrawals (about 1,180 Mgal/d during 1992 and 1,200 Mgal/d during 1993) were from surface-water sources. Nearly 70 percent of the fresh surface water was withdrawn in the Potomac River drainage basin. Most ground water (about 178 Mgal/d in 1992 and 194 Mgal/d in 1993) was withdrawn in the Upper Chesapeake drainage basin.The Potomac Group aquifers provided most of the ground water (about 61 Mgal/d during 1992 and 64 Mgal/d during 1993). Ten water-use categoriesrepresent the major demands on the surface-water and ground-water resources of the State: Public supply, domestic, commercial, industrial, mining, thermoelectric power, hydroelectric power, livestock, irrigation, and aquaculture. Largest withdrawals were for public supply (790 Mgal/d during 1992 and 812 Mgal/d during 1993), and the water was used by residences, commercial establishments, and industries. Baltimore City received the largest public-supply deliveries (about 126 Mgal/d during1992 and 129 Mgal/d during 1993). Freshwater withdrawals for self-supplied domestic, commercial, mining, aquaculture, and irrigation uses increased during the period, whereas withdrawals for industrial and thermoelectric power uses decreased.

[The role of computerized rheoencephalography in the assessment of normal pressure hydrocephalus. Preliminary report].

PubMed

Traczewski, Wojciech; Moskała, Marek; Szwabowska, Dorota; Gościński, Igor; Krupa, Mariusz; Polak, Jarosław

2005-01-01

It is generally agreed that the positive result of lumbar cerebrospinal fluid (CSF) withdrawal offers a reliable means for selection of patients likely to respond to shunting in normal pressure hydrocephalus (NPH). However the studies of cerebral hemodynamics in NPH are performed Routinely only in few neurosurgical centers. We therefore studied the effect of CSF withdrawal on cerebrovascular autoregulation (CVA) in this condition by means of computerized rheoencephalography [REG]. The study group consisted of 27 patients with presumed posttraumatic NPH. In each patient both the tap test and infusion test were performed. Psychometric tests and rheoencephalographic examinations were made twice: before and after CSF withdrawal. The obvious restoration of the functional state of CVA after CSF withdrawal was considered as a positive result of the tap test. Fourteen patients with a positive tap test and/or with resistance to CSF outflow (Rout) of more than 11 mmHg/ml/min were shunted. The improvement was obtained in 10 of them. Only one patient with a positive tap test did not improve. Our study suggests that restoration of CVA after CSF withdrawal is associated with high likelihood of shunt success, but not vice versa. Evaluation of CVA using REG seems to offer a new diagnostic tool in selecting patients likely to respond to shunting. Further studies are necessary to optimize the amount of CSF withdrawal, the delay between CSF withdrawal and control examinations and methodology of neuropsychological examinations.

Long-term effects of steroid withdrawal in kidney transplantation.

PubMed

Offermann, G; Schwarz, A; Krause, P H

1993-01-01

The long-term graft function after withdrawal of steroids from maintenance immunosuppression was analyzed in 98 kidney recipients (59 on cyclosporin monotherapy, 39 on cyclosporin plus azathioprine) who had not developed an early rejection episode when prednisolone was discontinued. Seven years after steroid withdrawal the probability of an increase in serum creatinine (> 20% of baseline levels) was 51%. The increase in creatinine was associated with sclerosing arteriopathy as a marker of chronic rejection in 29 of 43 graft biopsies. The addition of azathioprine had no effect on the stability of long-term graft function and did not influence the 7-year graft survival rate in this highly selected group of patients.

Electrophilic Triterpenoid Enones: A Comparative Thiol-Trapping and Bioactivity Study.

PubMed

Del Prete, Danilo; Taglialatela-Scafati, Orazio; Minassi, Alberto; Sirignano, Carmina; Cruz, Cristina; Bellido, Maria L; Muñoz, Eduardo; Appendino, Giovanni

2017-08-25

Bardoxolone methyl (1) is the quintessential member of triterpenoid cyanoacrylates, an emerging class of bioactive compounds capable of transient covalent binding to thiols. The mechanistic basis for this unusual "pulsed reactivity" profile and the mode of its biological translation are unknown. To provide clues on these issues, a series of Δ 1 -dehydrooleanolates bearing an electron-withdrawing group at C-2 (7a-m) were prepared from oleanolic acid (3a) and comparatively investigated in terms of reactivity with thiols and bioactivity against a series of electrophile-sensitive transcription factors (Nrf2, NF-κB, STAT3). The emerging picture suggests that the triterpenoid scaffold sharply decreases the reactivity of the enone system by steric encumbrance and that only strongly electrophilic and sterically undemanding substituents such as a cyanide or a carboxylate group can re-establish Michael reactivity, albeit in a transient way for the cyanide group. In general, a substantial dissection between the thiol-trapping ability and the modulation of biological end-points sensitive to thiol alkylation was observed, highlighting the role of shape complementarity for the activity of triterpenoid thia-Michael acceptors.

Synthesis, SAR and molecular docking studies of benzo[d]thiazole-hydrazones as potential antibacterial and antifungal agents.

PubMed

Zha, Gao-Feng; Leng, Jing; Darshini, N; Shubhavathi, T; Vivek, H K; Asiri, Abdullah M; Marwani, Hadi M; Rakesh, K P; Mallesha, N; Qin, Hua-Li

2017-07-15

A series of new benzo[d]thiazole-hydrazones analogues were synthesized and screened for their in vitro antibacterial and antifungal activities. The results revealed that compounds 13, 14, 15, 19, 20, 28 and 30 exhibited superior antibacterial potency compared to the reference drug chloramphenicol and rifampicin. Compounds 5, 9, 10, 11, 12, 28 and 30 were found to be good antifungal activity compared to the standard drug ketoconazole. A preliminary study of the structure-activity relationship (SAR) revealed that the antimicrobial activity depended on the effect of different substituents on the phenyl ring. The electron donating (OH and OCH 3 ) groups presented in the analogues, increase the antibacterial activity (except compound 12), interestingly, while the electron withdrawing (Cl, NO 2 , F and Br) groups increase the antifungal activity (except compound 19 and 20). In addition, analogues containing thiophene (28) and indole (30) showed good antimicrobial activities. Whereas, aliphatic analogues (24-26) shown no activities in both bacterial and fungal stains even in high concentrations (100µg/mL). Molecular docking studies were performed for all the synthesized compounds of which compounds 11, 19 and 20 showed the highest glide G-score. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment of Actual Chemical Wastewater by a Heterogeneous Fenton Process Using Natural Pyrite

PubMed Central

Sun, Liang; Li, Yan; Li, Aimin

2015-01-01

Wastewater from chemical plants has remarkable antibiotic effects on the microorganisms in traditional biological treatment processes. An enhanced Fenton system catalyzed by natural pyrite was developed to degrade this kind of wastewater. Approximately 30% chemical oxygen demand (COD) was removed within 120 min when 50 mmol/L H2O2 and 10 g/L natural pyrite were used at initial pH from 1.8 to 7. A BOD5/COD enhancement efficiency of 210% and an acute biotoxicity removal efficiency of 84% were achieved. The COD removal efficiency was less sensitive to initial pH than was the classic Fenton process. Excessive amounts of pyrite and H2O2 did not negatively affect the pyrite Fenton system. The amount of aniline generated indicated that nitrobenzene reduction by pyrite was promoted using a low initial concentration of H2O2 (<5 mmol/L). Fluorescence excitation emission matrix analyses illustrated that H2O2 facilitated the reduction by natural pyrite of organic molecules containing an electron-withdrawing group to electron-donating group. Thus, the Fenton-like process catalyzed by pyrite can remediate wastewater containing organic pollutants under mild reaction conditions and provide an alternative environmentally friendly method by which to reuse natural pyrite. PMID:26516893

Organocatalytic upgrading of furfural and 5-hydroxymethyl furfural to C10 and C12 furoins with quantitative yield and atom-efficiency.

PubMed

Zang, Hongjun; Chen, Eugene Y X

2015-03-30

There is increasing interest in the upgrading of C5 furfural (FF) and C6 5-hydroxymethyl furfural (HMF) into C10 and C12 furoins as higher energy-density intermediates for renewable chemicals, materials, and biofuels. This work utilizes the organocatalytic approach, using the in situ generated N,S-heterocyclic carbene catalyst derived from thiazolium ionic liquids (ILs), to achieve highly efficient self-coupling reactions of FF and HMF. Specifically, variations of the thiazolium IL structure have led to the most active and efficient catalyst system of the current series, which is derived from a new thiazolium IL carrying the electron-donating acetate group at the 5-ring position. For FF coupling by this IL (0.1 mol %, 60 °C, 1 h), when combined with Et3N, furoin was obtained in >99% yield. A 97% yield of the C12 furoin was also achieved from the HMF coupling by this catalyst system (10 mol % loading, 120 °C, 3 h). On the other hand, the thiazolium IL bearing the electron-withdrawing group at the 5-ring position is the least active and efficient catalyst. The mechanistic aspects of the coupling reaction by the thiazolium catalyst system have also been examined and a mechanism has been proposed.

Investigation of the Redox Chemistry of Anthraquinone Derivatives Using Density Functional Theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bachman, Jonathan E.; Curtiss, Larry A.; Assary, Rajeev S.

2014-09-25

Application of density functional calculations to compute electrochemical properties such as redox windows, effect of substitution by electron donating and electron withdrawing groups on redox windows, and solvation free energies for ~50 anthraquinone (AQ) derivatives are presented because of their potential as anolytes in all-organic redox flow batteries. Computations suggest that lithium ions can increase (by ~0.4 V) the reduction potential of anthraquinone due to the lithium ion pairing by forming a Lewis base-Lewis acid complex. To design new redox active species, the substitution by electron donating groups are essential to improve the reduction window of AQ with adequate oxidativemore » stability. For instance, a complete methylation of AQ can improve its reduction window by ~0.4 V. The quantum chemical studies of the ~50 AQ derivatives are used to derive a relationship that connects the computed LUMO energy and the reduction potential that can be applied as a descriptor for screening thousands of AQ derivatives. Our computations also suggest that incorporating oxy-methyl dioxolane substituents in the AQ framework can increase its interaction with non-aqueous solvent and improve its solubility. Thermochemical calculations for likely bond breaking decomposition reactions of un-substituted AQ anions suggest that the dianions are relatively stable in the solution. These studies provide ideal platform to perform further combined experimental and theoretical studies to understand the electrochemical reversibility and solubility of new quinone molecules as energy storage materials.« less

Adolescent Anabolic/Androgenic Steroids: Aggression and Anxiety During Exposure Predict Behavioral Responding During Withdrawal in Syrian Hamsters (Mesocricetus auratus)

PubMed Central

Ricci, Lesley A.; Morrison, Thomas R.; Melloni, Richard H.

2014-01-01

In the U.S. and worldwide anabolic/androgenic steroid use remains high in the adolescent population. This is concerning given that anabolic/androgenic steroid use is associated with a higher incidence of aggressive behavior during exposure and anxiety during withdrawal. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that an inverse behavioral relationship exists between anabolic/androgenic steroid-induced aggression and anxiety across adolescent exposure and withdrawal. In the first experiment, we examined aggression and anxiety during adolescent anabolic/androgenic steroid exposure and withdrawal. Adolescent anabolic/androgenic steroid administration produced significant increases in aggression and decreases in anxiety during the exposure period followed by significant decreases in aggression and increases in anxiety during anabolic/androgenic steroid withdrawal. In a second experiment, anabolic/androgenic steroid exposed animals were separated into groups based on their aggressive response during the exposure period and then tested for anxiety during exposure and then for both aggression and anxiety during withdrawal. Data were analyzed using a within subjects repeated measures predictive analysis. Linear regression analysis revealed that the difference in aggressive responding between the anabolic/androgenic steroid exposure and withdrawal periods was a significant predictor of differences in anxiety for both days of testing. Moreover, the combined data suggest that the decrease in aggressive behavior from exposure to withdrawal predicts an increase in anxiety-like responding within these same animals during this time span. Together these findings indicate that early anabolic/androgenic steroid exposure has potent aggression- and anxiety- eliciting effects and that these behavioral changes occur alongside a predictive relationship that exists between these two behaviors over time. PMID:24126136

Glucocorticoid receptors participate in the opiate withdrawal-induced stimulation of rats NTS noradrenergic activity and in the somatic signs of morphine withdrawal.

PubMed

Navarro-Zaragoza, Javier; Hidalgo, Juana M; Laorden, M Luisa; Milanés, M Victoria

2012-08-01

Recent evidence suggests that glucocorticoid receptor (GR) is a major molecular substrate of addictive properties of drugs of abuse. Hence, we performed a series of experiments to further characterize the role of GR signalling in opiate withdrawal-induced physical signs of dependence, enhanced noradrenaline (NA) turnover in the hypothalamic paraventricular nucleus (PVN) and tyrosine hydroxylase (TH) phosphorylation (activation) as well as GR expression in the nucleus of the solitary tract noradrenergic cell group (NTS-A₂). The role of GR signalling was assessed by i.p. pretreatment of the selective GR antagonist, mifepristone. Rats were implanted with two morphine (or placebo) pellets. Six days later, rats were pretreated with mifepristone or vehicle 30 min before naloxone and physical signs of abstinence, NA turnover, TH activation, GR expression and the hypothalamus-pituitary-adrenocortical axis activity were measured using HPLC, immunoblotting and RIA. Mifepristone alleviated the somatic signs of naloxone-induced opiate withdrawal. Mifepristone attenuated the increase in the NA metabolite, 3-methoxy-4-hydroxyphenylethylen glycol (MHPG), in the PVN, and the enhanced NA turnover observed in morphine-withdrawn rats. Mifepristone antagonized the TH phosphorylation at Ser³¹ and the expression of c-Fos expression induced by morphine withdrawal. Finally, naloxone-precipitated morphine withdrawal induced up-regulation of GR in the NTS. These results suggest that the physical signs of opiate withdrawal, TH activation and stimulation of noradrenergic pathways innervating the PVN are modulated by GR signalling. Overall, the present data suggest that drugs targeting the GR may ameliorate stress and aversive effects associated with opiate withdrawal. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Evidence for a causative role of N-methyl-D-aspartate receptors in an in vitro model of alcohol withdrawal hyperexcitability.

PubMed

Thomas, M P; Monaghan, D T; Morrisett, R A

1998-10-01

Synaptic mechanisms underlying hyperexcitability due to withdrawal from chronic ethanol exposure were investigated in a hippocampal explant model system using electrophysiological techniques. Whole-cell voltage clamp recordings from CA1 pyramidal cells demonstrated that acute ethanol exposure inhibited N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents by over 40%. Chronic ethanol exposure for 6 to 11 days at 35 or 75 mM induced no differences from control explants in the fast component of the population synaptic response (non-NMDAR-mediated). Prolonged field potential recordings (to 10 hr) were used to monitor the withdrawal process in vitro. Ethanol-exposed explants from both 35 and 75 mM groups displayed an increase (60% and 89%, respectively) in the NMDAR-mediated component of synaptic transmission on withdrawal from chronic exposure. Prolonged tonic-clonic electrographic seizure activity was consistently observed after ethanol withdrawal only after the increase in NMDAR function. This hyperexcitability was inhibited by the NMDAR antagonist D-2-amino-5-phosphonovaleric acid and returned once the NMDAR component was reestablished after antagonist washout. In situ hybridization studies suggest that expression of NR2B subunit mRNA may be enhanced in explants after chronic ethanol exposure. No lasting differences were observed in the NMDAR component after acute in vitro ethanol exposure and withdrawal. These data suggest that the occurance of ethanol withdrawal hyperexcitability in this system may be directly dependent on alterations in NMDAR function after chronic exposure. Since this region and others that contain ethanol sensitive NMDARs may serve as epileptic foci, long term alterations in NMDAR function may be expected to generate paroxysmal depolarizing shifts underlying ictal events after withdrawal from ethanol exposure.

Lithium carbonate in the management of cannabis withdrawal: a randomized placebo-controlled trial in an inpatient setting.

PubMed

Johnston, Jennifer; Lintzeris, Nicholas; Allsop, David J; Suraev, Anastasia; Booth, Jessica; Carson, Dean S; Helliwell, David; Winstock, Adam; McGregor, Iain S

2014-12-01

Preclinical studies suggest that lithium carbonate (lithium) can reduce precipitated cannabinoid withdrawal in rats by stimulating release of the neuropeptide oxytocin, while two open-label studies indicate lithium may ameliorate cannabis withdrawal symptoms in humans. This study was conducted to examine the efficacy and safety of lithium in the inpatient management of cannabis withdrawal and to determine whether lithium affects plasma oxytocin and the rate of elimination of plasma cannabinoids during abstinence. Treatment-seeking cannabis-dependent adults (n = 38) were admitted for 8 days to an inpatient withdrawal unit and randomized to either oral lithium (500 mg) or placebo given twice a day under double-blind randomized controlled trial (RCT) conditions. Primary outcomes included withdrawal severity [cannabis withdrawal scale (CWS)], rates of detoxification completion, and adverse events. Plasma cannabinoids, plasma oxytocin and serum lithium levels were measured repeatedly over admission. Follow-up research interviews were conducted at 14, 30, and 90 days postdischarge. Lithium did not significantly affect total CWS scores relative to placebo, although it significantly reduced individual symptoms of "loss of appetite," "stomach aches," and "nightmares/strange dreams." No significant group differences were found in treatment retention or adverse events. Lithium did not increase plasma oxytocin levels nor influence the rate of elimination of cannabinoids. Both placebo- and lithium-treated participants showed reduced levels of cannabis use (verified by urinalysis) and improved health and psychosocial outcomes at 30- and 90-day follow-up relative to pretreatment baselines. Despite the strong rationale for the present study, the efficacy of lithium over placebo in the management of cannabis withdrawal was not demonstrated.

Systematic meta-analysis of childhood social withdrawal in schizophrenia, and comparison with data from at-risk children aged 9-14 years.

PubMed

Matheson, Sandra L; Vijayan, Hena; Dickson, Hannah; Shepherd, Alana M; Carr, Vaughan J; Laurens, Kristin R

2013-08-01

Social withdrawal is a robust childhood risk factor for later schizophrenia. The aims of this paper were to assess the evidence for childhood social withdrawal among adults with schizophrenia and, comparatively, in children aged 9-14 years who are putatively at-risk of developing schizophrenia. We conducted a meta-analysis, including cohort and case-control studies reporting social withdrawal measured by the Child Behavior Checklist (CBCL) in adults with schizophrenia vs. controls. Further, an experimental study compared CBCL withdrawal scores from typically-developing children with scores from two groups of putatively at-risk children: (i) children displaying a triad of replicated antecedents for schizophrenia, and (ii) children with at least one first- or second-degree relative with schizophrenia or schizoaffective disorder. Six studies met inclusion criteria for the meta-analysis (N = 3828), which demonstrated a large effect of increased childhood social withdrawal in adults with schizophrenia (standardized mean difference [SMD] score = 1.035, 95% CI = 0.304-1.766, p = 0.006), with no indication of publication bias, but considerable heterogeneity (I(2) = 91%). Results from the experimental study also indicated a large effect of increased social withdrawal in children displaying the antecedent triad (SMD = 0.743, p = 0.001), and a weaker effect in children with a family history of schizophrenia (SMD = 0.442, p = 0.051). Childhood social withdrawal may constitute a vulnerability marker for schizophrenia in the presence of other antecedents and/or genetic risk factors for schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Effect of Motivational Interviewing on Craving and Dependence on Hookah in Suburban Pregnant Women in South East of Iran.

PubMed

Mojahed, Kheirolnesa; Navidian, Ali

2018-05-30

Hookah smoking during pregnancy is a health concern which requires effective interventions. Thus, the authors have aimed to evaluate the effect of motivational interviewing on craving and dependence on hookah in pregnant women (n = 140) addicted to hookah who reside in the outskirts of Zahedan, a city in southeast of Iran. The subjects were selected using the convenience sampling and randomly divided into either the control or intervention group. The intervention group received five motivational interviewing group sessions about hookah smoking withdrawal, whereas the control group was given the conventional recommendations for quitting hookah. Data were collected after eight weeks during the post intervention period using Hookah Craving Test and Hookah Addiction Severity Index. Next, they were analyzed using independent t-test, paired t-test, and analysis of covariance (ANCOVA). After the motivational interviewing intervention, the independent t-test indicated a significant difference between the intervention and control groups in terms of the mean score of hookah craving (P = 0.0001). Moreover, ANCOVA, with control of the effect of pretest and duration of hookah addiction, demonstrated a significant difference between the two groups regarding the mean score of hookah dependence after the intervention (P = 0.0001). Motivational interviewing had a significant positive impact on decreased hookah craving and dependence (two indices of withdrawal). Therefore, healthcare providers are recommended to incorporate motivational interviewing-based education into prenatal care programs to promote the chance of hookah smoking withdrawal.

Benzimidazobenzothiazole-based highly-efficient thermally activated delayed fluorescence emitters for organic light-emitting diodes: A quantum-chemical TD-DFT study

NASA Astrophysics Data System (ADS)

Zhu, Qiuling; Wen, Keke; Feng, Songyan; Guo, Xugeng; Zhang, Jinglai

2018-03-01

Based upon two thermally activated delayed fluorescence (TADF) emitters 1 and 2, compounds 3-6 have been designed by replacing the carbazol group with the bis(4-biphenyl)amine one (3 and 4) and introducing the electron-withdrawing CF3 group into the acceptor unit of 3 and 4 (5 and 6). It is found that the present calculations predict comparable but relatively large energy differences (approximate 0.5 eV) between the lowest singlet S1 and triplet T1 states (Δ EST) for the six targeted compounds. In order to explain the highly-efficient TADF behavior observed in compounds 1 and 2, the"triplet reservoir" mechanism has been proposed. In addition, the fluorescence rates of all six compounds are very large, in 107-108 orders of magnitude. According to the present calculations, it is a reasonable assumption that the newly designed compounds 3-6 could be considered as the potential TADF emitters, which needs to be further verified by experimental techniques.

D-A-D-Typed Hole Transport Materials for Efficient Perovskite Solar Cells: Tuning Photovoltaic Properties via the Acceptor Group.

PubMed

Xu, Peng; Liu, Peng; Li, Yuanyuan; Xu, Bo; Kloo, Lars; Sun, Licheng; Hua, Yong

2018-06-13

Two D-A-D-structured hole-transport materials (YN1 and YN2) have been synthesized and used in perovskite solar cells. The two HTMs have low-lying HOMO levels and impressive mobility. Perovskite-based solar cells (PSCs) fabricated with YN2 showed a power conversion efficiency (PCE) value of 19.27% in ambient air, which is significantly higher than that of Spiro-OMeTAD (17.80%). PSCs based on YN1 showed an inferior PCE of 16.03%. We found that the incorporation of the stronger electron-withdrawing group in the HTM YN2 improves the PCE of PSCs. Furthermore, the YN2-based PSCs exhibit good long-term stability retaining 91.3% of its initial efficiency, whereas PSCs based on Spiro-OMeTAD retained only 42.2% after 1000 h lifetime (dark conditions). These promising results can provide a new strategy for the design of D-A-D HTMs for PSC applications in future.

Combined 3D-QSAR modeling and molecular docking study on azacycles CCR5 antagonists

NASA Astrophysics Data System (ADS)

Ji, Yongjun; Shu, Mao; Lin, Yong; Wang, Yuanqiang; Wang, Rui; Hu, Yong; Lin, Zhihua

2013-08-01

The beta chemokine receptor 5 (CCR5) is an attractive target for pharmaceutical industry in the HIV-1, inflammation and cancer therapeutic areas. In this study, we have developed quantitative structure activity relationship (QSAR) models for a series of 41 azacycles CCR5 antagonists using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and Topomer CoMFA methods. The cross-validated coefficient q2 values of 3D-QASR (CoMFA, CoMSIA, and Topomer CoMFA) methods were 0.630, 0.758, and 0.852, respectively, the non-cross-validated R2 values were 0.979, 0.978, and 0.990, respectively. Docking studies were also employed to determine the most probable binding mode. 3D contour maps and docking results suggested that bulky groups and electron-withdrawing groups on the core part would decrease antiviral activity. Furthermore, docking results indicated that H-bonds and π bonds were favorable for antiviral activities. Finally, a set of novel derivatives with predicted activities were designed.

Blue phosphorescent nitrile containing C^C* cyclometalated NHC platinum(II) complexes.

PubMed

Tronnier, Alexander; Metz, Stefan; Wagenblast, Gerhard; Muenster, Ingo; Strassner, Thomas

2014-02-28

Since C^C* cyclometalated Pt(II) complexes with N-heterocyclic carbene (NHC) ligands have been identified as potential emitter materials in organic light-emitting devices (OLEDs), very promising results regarding quantum yields, colour and stability have been presented. Herein, we report on four nitrile substituted complexes with a chelating NHC ligand (1-(4-cyanophenyl)-3-isopropyl-1H-benzo[d]imidazole or 4-(tert-butyl)-1-(4-cyanophenyl)-3-methyl-1H-imidazole) and a bidentate monoanionic auxiliary ligand (acetylacetone or dimesitoylmethane). The complexes have been fully characterized including extensive 2D NMR studies (COSY, HSQC, HMBC, NOESY, (195)Pt NMR), three of them also by solid-state structures. Photophysical measurements in amorphous PMMA films and pure emitter films at room temperature reveal the impact of the mesityl groups in the auxiliary ligand, which led to a significant increase of the quantum yield, while the decay lifetimes decreased. The electron withdrawing nitrile groups shift the emission towards blue colour coordinates.

Design, synthesis, and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators.

PubMed

Zhang, Xuqing; Li, Xiaojie; Allan, George F; Sbriscia, Tifanie; Linton, Olivia; Lundeen, Scott G; Sui, Zhihua

2007-08-09

A novel series of pyrazolines 2 have been designed, synthesized, and evaluated by in vivo screening as tissue-selective androgen receptor modulators (SARMs). Structure-activity relationships (SAR) were investigated at the R1 to R6 positions as well as the core pyrazoline ring and the anilide linker. Overall, strong electron-withdrawing groups at the R1 and R2 positions and a small group at the R5 and R6 position are optimal for AR agonist activity. The (S)-isomer of 7c exhibits more potent AR agonist activity than the corresponding (R)-isomer. (S)-7c exhibited an overall partial androgenic effect but full anabolic effect via oral administration in castrated rats. It demonstrated a noticeable antiandrogenic effect on prostate in intact rats with endogenous testosterone. Thus, (S)-7c is a tissue-selective nonsteroidal androgen receptor modulator with agonist activity on muscle and mixed agonist and antagonist activity on prostate.

A randomised, crossover study on an electronic vapour product, a nicotine inhalator and a conventional cigarette. Part B: Safety and subjective effects.

PubMed

Walele, Tanvir; Sharma, Girish; Savioz, Rebecca; Martin, Claire; Williams, Josie

2016-02-01

An Electronic Vapour Product (EVP) has been evaluated for short-term safety parameters and subjective effects in a 2-part study, in smokers. Part 1 compared the EVP with unflavoured (UF) and flavoured (FL) e-liquid at 2.0% nicotine to a conventional cigarette (CC; JPS Silver King Size, 0.6 mg) and a licensed nicotine inhalator (Nicorette(®), 15 mg). Part 2 assessed the effect of increasing concentrations of nicotine in the e-liquid used with the EVP (0%, 0.4%, 0.9%, 2.0%). The study was designed as a randomised, controlled, crossover trial. Outcomes included adverse events (AEs), vital signs, exhaled carbon monoxide (CO), clinical laboratory parameters, smoking urges and withdrawal symptoms. In both study parts, only mild non-serious AEs were reported. No major differences were observed in AEs between the EVPs and Nicorette(®). Exhaled CO levels only increased for CC. All products appeared to decrease smoking urges and nicotine withdrawal symptom scores to a similar extent. The EVP had a similar short-term safety profile to Nicorette(®) and relieved smoking urges and nicotine withdrawal symptoms to a similar extent as Nicorette(®) and CC. Unlike nicotine replacement therapies, the EVP may offer an alternative for those finding it difficult to quit the behavioural and sensorial aspects of smoking. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Trans influence on the rate of reductive elimination. Reductive elimination of amines from isomeric arylpalladium amides with unsymmetrical coordination spheres.

PubMed

Yamashita, Makoto; Cuevas Vicario, Jose V; Hartwig, John F

2003-12-31

To determine the trans effect on the rates of reductive eliminations from arylpalladium(II) amido complexes, the reactions of arylpalladium amido complexes bearing symmetrical and unsymmetrical DPPF (DPPF = bis(diphenylphosphino)ferrocene) derivatives were studied. THF solutions of LPd(Ar)(NMeAr') (L = DPPF, DPPF-OMe, DPPF-CF3, DPPF-OMe,Ph, DPPF-Ph,CF3, and DPPF-OMe,CF3; Ar = C6H4-4-CF3; Ar' = C6H4-4-CH3, Ph, and C6H4-4-OMe) underwent C-N bond forming reductive elimination at -15 C to form the corresponding N-methyldiarylamine in high yield. Complexes ligated by symmetrical DPPF derivatives with electron-withdrawing substituents on the DPPF aryl groups underwent reductive elimination faster than complexes ligated by symmetrical DPPF derivatives with electron-donating substituents on the ligand aryl groups. Studies of arylpalladium amido complexes containing unsymmetrical DPPF ligands revealed several trends. First, the complex with the weaker donor trans to nitrogen and the stronger donor trans to the palladium-bound aryl group underwent reductive elimination faster than the regioisomeric complex with the stronger donor trans to nitrogen and the weaker donor trans to the palladium-bound aryl group. Second, the effect of varying the substituents on the phosphorus donor trans to the nitrogen was larger than the effect of varying the substituents on the phosphorus donor trans to the palladium-bound aryl group. Third, the difference in rate between the isomeric arylpalladium amido complexes was similar in magnitude to the differences in rates resulting from conventional variation of substituents on the symmetric phosphine ligands. This result suggests that the geometry of the complex is equal in importance to the donating ability of the dative ligands. The ratio of the differences in rates of reaction of the isomeric complexes was similar to the relative populations of the two geometric isomers. This result and consideration of transition state geometries suggest that the reaction rates are controlled more by substituent effects on ground state stability than on transition state energies. In addition, variation of the aryl group at the amido nitrogen showed systematically that complexes with more electron-donating groups at nitrogen undergo faster reductive elimination than those with less electron-donating groups at nitrogen.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christopher M. Leavitt; Garold L. Gresham; Michael T. Benson

Diphenyldithiophosphinate (DTP) ligands modified with electron-withdrawing trifluoromethyl (TFM) substitutents are of high interest because they have demonstrated potential for exceptional separation of Am3+ from lanthanide3+ cations. Specifically, the bis(ortho-TFM) (L1-) and (ortho-TFM)(meta-TFM) (L2-) derivatives have shown excellent separation selectivity, while the bis(meta-TFM) (L3)- and unmodified DTP (Lu-) did not. Factors responsible for selective coordination have been investigated using density functional theory (DFT) calculations in concert with competitive dissociation reactions in the gas phase. To evaluate the role of (DTP+H) acidity, density functional calculations were used to predict pKa values, which followed the trend of L3 < L2 < L1 L1- > L2- > L3-.« less

Palonosetron and Hydroxyzine Pre-treatment Reduces the Objective Signs of Experimentally-Induced Acute Opioid Withdrawal in Humans: A Double-Blinded, Randomized, Placebo-Controlled Crossover Study

PubMed Central

Erlendson, Matthew; D'Arcy, Nicole; Encisco, Ellen; Yu, Jeff; Rincon-Cruz, Lorena; Peltz, Gary; Clark, J. David

2017-01-01

Background Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective. Objectives This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect. Methods At timepoint T=0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T=30 by intravenous morphine (10mg/70kg). At T=165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T=170, 180, respectively). Baseline measurements were recorded at T=-30 and T=-15. Results Comparison of average baseline OOWS scores with OOWS scores obtained fifteen minutes after naloxone was significant (p=0.0001). Scores from fifteen minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5± 0.97; and palonosetron with hydroxyzine, 0.2 ± .1333. Conclusions Pretreatment with palonosetron significantly reduced many signs of experimental-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal. PMID:27712113

Changes in Serum Biochemical Factors Associated with Opium Addiction after Addiction Desertion

PubMed Central

Afarinesh, Mohammad Reza; Haghpanah, Tahereh; Divsalar, Kouros; Dehyadegary, Elham; Shaikh-Aleslami, Azar; Mahmoodi, Majid

2014-01-01

Background The long time use of opium has some effects on serums biochemical factors, the determination of this variation is a new approach in understanding off addiction and relive of drug abuser health. Hence in this study, these indicators in person who were withdrawing of opium have been studied. Methods In this cross-sectional study bloods biochemical factors such as fasting blood sugar (FBS), sodium (Na), calcium (Ca), uric acid (UA), blood urea nitrogen (BUN), creatinine, cholesterol, total protein, and fibrinogen in three groups serum were studied: (1) Who had been permanent opium users more than 2 years (case). (2) Dependent person who has taken one month addiction withdrawal course (control). (3) A healthy group that had been demographically similar to the other groups. Findings According to these study findings, FBS serum level in the case group is lower than control group. Serum level of Na, creatinine, and blood triglyceride (TG) in case study are higher than group control. Concentration of potassium, Ca, UA, BUN, cholesterol, total serum protein, fibrinogen, and thrombin time in case study and group control showed no significant difference. Also, in withdrawing case serum level of Na, Ca, UA, BUN, creatinine, and TG significantly increase and thrombin time decrease. Conclusion According to this study not only the longtime use of opium but also opium with drawerin opium dependent people can change their serum biochemical factors. So recognition, treatment, and prevention of this change could be a new step in improving of health and condition of patients. PMID:25984281

Group hypnosis vs. relaxation for smoking cessation in adults: a cluster-randomised controlled trial

PubMed Central

2013-01-01

Background Despite the popularity of hypnotherapy for smoking cessation, the efficacy of this method is unclear. We aimed to investigate the efficacy of a single-session of group hypnotherapy for smoking cessation compared to relaxation in Swiss adult smokers. Methods This was a cluster-randomised, parallel-group, controlled trial. A single session of hypnosis or relaxation for smoking cessation was delivered to groups of smokers (median size = 11). Participants were 223 smokers consuming ≥ 5 cigarettes per day, willing to quit and not using cessation aids (47.1% females, M = 37.5 years [SD = 11.8], 86.1% Swiss). Nicotine withdrawal, smoking abstinence self-efficacy, and adverse reactions were assessed at a 2-week follow-up. The main outcome, self-reported 30-day point prevalence of smoking abstinence, was assessed at a 6-month follow up. Abstinence was validated through salivary analysis. Secondary outcomes included number of cigarettes smoked per day, smoking abstinence self-efficacy, and nicotine withdrawal. Results At the 6-month follow up, 14.7% in the hypnosis group and 17.8% in the relaxation group were abstinent. The intervention had no effect on smoking status (p = .73) or on the number of cigarettes smoked per day (p = .56). Smoking abstinence self-efficacy did not differ between the interventions (p = .14) at the 2-week follow-up, but non-smokers in the hypnosis group experienced reduced withdrawal (p = .02). Both interventions produced few adverse reactions (p = .81). Conclusions A single session of group hypnotherapy does not appear to be more effective for smoking cessation than a group relaxation session. Trial registration Current Controlled Trials ISRCTN72839675. PMID:24365274

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park Y. S.; Kale, T.; Wu, Q.

A series of diketopyrrolopyrrole(DPP)-based small molecules have been synthesized by palladium-catalyzed coupling reactions. Electron-donating moieties (benzothiophene, benzoselenophene, and benzotellurophene) are bridged by an electron-withdrawing DPP unit to generate donor-acceptor-donor (D-A-D) type molecules. We observe red-shifts in absorption spectra of these compounds by varying heteroatoms from sulfur to tellurium. In bulk heterojunction solar cells with [6,6]phenyl-C61-butyric acid methyl ester (PC61BM) as acceptor, we obtain power conversion efficiencies of 2.4% (benzothiophene), 4.1% (benzoselenophene), and 3.0% (benzotellurophene), respectively.

Substituent Effects on the Self-Assembly/Coassembly and Hydrogelation of Phenylalanine Derivatives.

PubMed

Liyanage, Wathsala; Nilsson, Bradley L

2016-01-26

Supramolecular hydrogels derived from the self-assembly of organic molecules have been exploited for applications ranging from drug delivery to tissue engineering. The relationship between the structure of the assembly motif and the emergent properties of the resulting materials is often poorly understood, impeding rational approaches for the creation of next-generation materials. Aromatic π-π interactions play a significant role in the self-assembly of many supramolecular hydrogelators, but the exact nature of these interactions lacks definition. Conventional models that describe π-π interactions rely on quadrupolar electrostatic interactions between neighboring aryl groups in the π-system. However, recent experimental and computational studies reveal the potential importance of local dipolar interactions between elements of neighboring aromatic rings in stabilizing π-π interactions. Herein, we examine the nature of π-π interactions in the self- and coassembly of Fmoc-Phe-derived hydrogelators by systematically varying the electron-donating or electron-withdrawing nature of the side chain benzyl substituents and correlating these effects to the emergent assembly and gelation properties of the systems. These studies indicate a significant role for stabilizing dipolar interactions between neighboring benzyl groups in the assembled materials. Additional evidence for specific dipolar interactions is provided by high-resolution crystal structures obtained from dynamic transition of gel fibrils to crystals for several of the self-assembled/coassembled Fmoc-Phe derivatives. In addition to electronic effects, steric properties also have a significant effect on the interaction between neighboring benzyl groups in these assembled systems. These findings provide significant insight into the structure-function relationship for Fmoc-Phe-derived hydrogelators and give cues for the design of next-generation materials with desired emergent properties.

Integrating theory, synthesis, spectroscopy and device efficiency to design and characterize donor materials for organic photovoltaics: a case study including 12 donors

DOE PAGES

Oosterhout, S. D.; Kopidakis, N.; Owczarczyk, Z. R.; ...

2015-04-07

There have been remarkable improvements in the power conversion efficiency of solution-processable Organic Photovoltaics (OPV) have largely been driven by the development of novel narrow bandgap copolymer donors comprising an electron-donating (D) and an electron-withdrawing (A) group within the repeat unit. The large pool of potential D and A units and the laborious processes of chemical synthesis and device optimization, has made progress on new high efficiency materials slow with a few new efficient copolymers reported every year despite the large number of groups pursuing these materials. In our paper we present an integrated approach toward new narrow bandgap copolymersmore » that uses theory to guide the selection of materials to be synthesized based on their predicted energy levels, and time-resolved microwave conductivity (TRMC) to select the best-performing copolymer–fullerene bulk heterojunction to be incorporated into complete OPV devices. We validate our methodology by using a diverse group of 12 copolymers, including new and literature materials, to demonstrate good correlation between (a) theoretically determined energy levels of polymers and experimentally determined ionization energies and electron affinities and (b) photoconductance, measured by TRMC, and OPV device performance. The materials used here also allow us to explore whether further copolymer design rules need to be incorporated into our methodology for materials selection. For example, we explore the effect of the enthalpy change (ΔH) during exciton dissociation on the efficiency of free charge carrier generation and device efficiency and find that ΔH of -0.4 eV is sufficient for efficient charge generation.« less

Can nitro groups really anchor onto TiO 2? Case study of dye-to-TiO 2 adsorption using azo dyes with NO 2 substituents

DOE PAGES

Zhang, Lei; Cole, Jacqueline M.

2016-06-21

The nitro group has recently been suggested as a new type of anchor for dye-sensitized solar cells (DSSCs) and has shown promising optoelectronic properties. Considering the excellent electron withdrawing ability of the nitro group and wider materials selection brought about by this substituent, it is helpful to evaluate the interfacial structures and photophysics of more organic dyes where NO 2 poses as the dye-to-TiO 2 anchor. A computational study on a family of azo dyes bearing a nitro group is presented in this paper, where the effect of certain side groups on their optical properties is examined. Both isolated dyemore » molecules and dye/TiO 2 nanocomposites are studied via density functional theory and time-dependent density functional theory, with complementary experimental UV/vis absorption spectroscopy and photovoltaic device testing. Results demonstrate that these nitro-containing dyes prefer a monodentate anchoring mode on a TiO 2 cluster. These nitro dyes reveal weak, but non-negligible, adsorption onto TiO 2; yet, very low photovoltaic performance once incorporated into a DSSC device. Finally, this poor delivery of nitro groups as DSSC anchors is ostensibly inconsistent with previous findings; but is rationalized via the “auxiliary anchor” concept.« less

Epigenetic modification: possible approach to reduce Salmonella enterica serovar enteritidis susceptibility under stress conditions.

PubMed

Soleimani, A F; Zulkifli, I; Hair-Bejo, M; Ebrahimi, M; Jazayeri, S D; Hashemi, S R; Meimandipour, A; Goh, Y M

2012-01-01

Stressors may influence chicken susceptibility to pathogens such as Salmonella enterica. Feed withdrawal stress can cause changes in normal intestinal epithelial structure and may lead to increased attachment and colonization of Salmonella. This study aimed to investigate modulatory effects of epigenetic modification by feed restriction on S. enterica serovar Enteritidis colonization in broiler chickens subjected to feed withdrawal stress. Chicks were divided into four groups: ad libitum feeding; ad libitum feeding with 24-h feed withdrawal on day 42; 60% feed restriction on days 4, 5, and 6; and 60% feed restriction on days 4, 5, and 6 with 24-h feed withdrawal on day 42. Attachment of S. Enteritidis to ileal tissue was determined using an ex vivo ileal loop assay, and heat shock protein 70 (Hsp70) expression was evaluated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blotting. Feed withdrawal stress increased S. Enteritidis attachment to ileal tissue. However, following feed withdrawal the epigenetically modified chickens had significantly lower attachment of S. Enteritidis than their control counterparts. A similar trend with a very positive correlation was observed for Hsp70 expression. It appears that epigenetic modification can enhance resistance to S. Enteritidis colonization later in life in chickens under stress conditions. The underlying mechanism could be associated with the lower Hsp70 expression in the epigenetically modified chickens.

Social withdrawal of persons with vascular dementia associated with disturbance of basic daily activities, apathy, and impaired social judgment.

PubMed

Honda, Yukiko; Meguro, Kenichi; Meguro, Mitsue; Akanuma, Kyoko

2013-01-01

Patients with vascular dementia (VaD) are often isolated, withdrawn from society because of negative symptoms and functional disabilities. The aim of this study was to detect factors associated with social withdrawal in patients with VaD. The participants were 36 institutionalized patients with VaD. Social withdrawal was assessed with the social withdrawal of the Multidimensional Observation Scale for Elderly Subjects (MOSES). Possible explanatory variables were the MOSES items depression and self-care, Cognitive Abilities Screening Instrument (CASI), apathy evaluation scale (AES), and Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW). Multiple regression analyses were conducted for two groups: Analysis 1 was performed in all patients (N = 36) and Analysis 2 was performed in the patients with the ability to move by themselves (i.e., independent walking or independent movement with a cane or a wheelchair; n = 28). In Analysis 1, MOSES item social withdrawal was correlated with AES and MOSES item self-care. In Analysis 2, MOSES item social withdrawal was correlated with AES and CASI domain abstraction and judgment. Decreased social activities of VaD were not related to general cognitive function or depression. Disturbed activities of daily living (ADLs) for self-care may involve decreased frontal lobe function, indicating that comprehensive rehabilitation for both ADL and dementia are needed to improve the social activities of patients with VaD.

Spectroscopic, Electrochemical and DFT Studies of Phosphorescent Homoleptic Cyclometalated Iridium(III) Complexes Based on Substituted 4-Fluorophenylvinyl- and 4-Methoxyphenylvinylquinolines

PubMed Central

Adeloye, Adewale O.; Adekunle, Abolanle S.; Ramasami, Ponnadurai

2017-01-01

This study reports the synthesis and comparative investigation of the substituent effects of a new series of highly luminescent homoleptic tris-cyclometalated iridium(III) complexes of the type [Ir(N˄C)3]. These are based on two ligand type derivatives comprising of 4-fluorophenylvinylquinolines and 4-methoxyphenylvinylquinolines with electron-donating and/or electron-withdrawing groups as aryl substituents at 2-position. The structures of the ligands and their complexes were characterized by means of FT-IR, UV-Vis and NMR spectrometry complemented with photoluminescence and cyclic voltammetry. The photophysical properties of 2-aryl-4-(4-fluorophenylvinyl)quinoline and its corresponding complex were also studied using the density functional theory method. The photoluminescent properties of the ligands and the corresponding complexes showed high fluorescent intensities and quantum yields in solvents of different polarities. The photoluminescence spectra of the complexes in solid film, showed common transmission curves at longer wavelengths maximum (λem = 697 nm) possibly originating from the interference of scattered light of higher-order transmission of monochromators. PMID:28934145

Spectroscopic, Electrochemical and DFT Studies of Phosphorescent Homoleptic Cyclometalated Iridium(III) Complexes Based on Substituted 4-Fluorophenylvinyl- and 4-Methoxyphenylvinylquinolines.

PubMed

Adeloye, Adewale O; Mphahlele, Malose J; Adekunle, Abolanle S; Rhyman, Lydia; Ramasami, Ponnadurai

2017-09-21

This study reports the synthesis and comparative investigation of the substituent effects of a new series of highly luminescent homoleptic tris-cyclometalated iridium(III) complexes of the type [Ir(N ˄ C)₃]. These are based on two ligand type derivatives comprising of 4-fluorophenylvinylquinolines and 4-methoxyphenylvinylquinolines with electron-donating and/or electron-withdrawing groups as aryl substituents at 2-position. The structures of the ligands and their complexes were characterized by means of FT-IR, UV-Vis and NMR spectrometry complemented with photoluminescence and cyclic voltammetry. The photophysical properties of 2-aryl-4-(4-fluorophenylvinyl)quinoline and its corresponding complex were also studied using the density functional theory method. The photoluminescent properties of the ligands and the corresponding complexes showed high fluorescent intensities and quantum yields in solvents of different polarities. The photoluminescence spectra of the complexes in solid film, showed common transmission curves at longer wavelengths maximum (λ em = 697 nm) possibly originating from the interference of scattered light of higher-order transmission of monochromators.

Design and synthesis of oxymatrine analogues overcoming drug resistance in hepatitis B virus through targeting host heat stress cognate 70.

PubMed

Gao, Li-Mei; Han, Yan-Xing; Wang, Yu-Ping; Li, Yu-Huan; Shan, Yong-Qiang; Li, Xin; Peng, Zong-Gen; Bi, Chong-Wen; Zhang, Tian; Du, Na-Na; Jiang, Jian-Dong; Song, Dan-Qing

2011-02-10

Heat-stress cognate 70 (Hsc70) is a host protein required for hepatitis B virus (HBV) replication, and oxymatrine (1) suppresses Hsc70 expression. Taking Hsc70 as a target against HBV, 22 analogues of 1 defined with substituents at position 1, 13, or 14 were synthesized and evaluated for their activity on Hsc70 mRNA expression. The SAR revealed that (i) the oxygen atom at the 1-position was not essential, (ii) increasing electron density on the ring D reduced the activity, and (iii) introducing a proper substituent at the 13- and/or 14-position(s), especially electron-withdrawing groups, might enhance the activity. Among the analogues, 6b possessing 13-ethoxyl afforded an increased activity in respect to 1. Importantly, it was active for either wild-type or lamivudine-resistant HBV, as its target is host Hsc70 but not viral enzymes. LD(50) of 6b in mice was over 750 mg/kg in oral route. We consider compound 6b promising for further investigation.

Thiazole-based organic semiconductors for organic electronics.

PubMed

Lin, Yuze; Fan, Haijun; Li, Yongfang; Zhan, Xiaowei

2012-06-19

Over the past two decades, organic semiconductors have been the subject of intensive academic and commercial interests. Thiazole is a common electron-accepting heterocycle due to electron-withdrawing nitrogen of imine (C=N), several moieties based on thiazole have been widely introduced into organic semiconductors, and yielded high performance in organic electronic devices. This article reviews recent developments in the area of thiazole-based organic semiconductors, particularly thiazole, bithiazole, thiazolothiazole and benzobisthiazole-based small molecules and polymers, for applications in organic field-effect transistors, solar cells and light-emitting diodes. The remaining problems and challenges, and the key research direction in near future are discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.